Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence

Bronchopulmonary dysplasia (BPD) is one of the most frequent complications in extremely low gestational age neonates, but has remained largely unchanged in rate. We reviewed data on BPD prevention focusing on recent meta-analyses. Interventions with proven effectiveness in reducing BPD include the primary use of non-invasive respiratory support, the application of surfactant without endotracheal ventilation and the use of volume-targeted ventilation in infants requiring endotracheal intubation. Following extubation, synchronised nasal ventilation is more effective than continuous positive airway pressure in reducing BPD. Pharmacologically, commencing caffeine citrate on postnatal day 1 or 2 seems more effective than a later start. Applying intramuscular vitamin A for the first 4 weeks reduces BPD, but is expensive and painful and thus not widely used. Low-dose hydrocortisone for the first 10 days prevents BPD, but was associated with almost twice as many cases of late-onset sepsis in infants born at 24–25 weeks’ gestation. Inhaled corticosteroids, despite reducing BPD, were associated with a higher mortality rate. Administering dexamethasone to infants still requiring mechanical ventilation around postnatal weeks 2–3 may represent the best trade-off between restricting steroids to infants at risk of BPD while still affording high efficacy. Finally, identifying infants colonised with ureaplasma and treating those requiring intubation and mechanical ventilation with azithromycin is another promising approach to BPD prevention. Further interventions yet only backed by cohort studies include exclusive breastmilk feeding and a better prevention of nosocomial infections.

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The association between clinical and biochemical characteristics of late-onset sepsis and bronchopulmonary dysplasia in preterm infants

European Journal of Pediatrics ◽

10.1007/s00431-021-03981-9 ◽

2021 ◽

Author(s):

Melania E. Ebrahimi ◽

Michelle Romijn ◽

Roos J. S. Vliegenthart ◽

Douwe H. Visser ◽

Anton H. van Kaam ◽

...

Keyword(s):

Mechanical Ventilation ◽

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Gestational Age ◽

Late Onset ◽

Multivariate Logistic Regression Analysis ◽

Biochemical Characteristics ◽

Late Onset Sepsis ◽

Early Onset Sepsis ◽

Increased Risk

AbstractStudies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known:• Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia• This association is mainly shown in infants with a positive blood culture What is New:• This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia• The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

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Prolonged empiric antibiotics and time to full enteral feed in preterm infants less than 29 weeks of gestational age

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-200555 ◽

2021 ◽

pp. 1-5

Author(s):

M.R. Alturk ◽

H. Salama ◽

H. Al Rifai ◽

M. Al Qubaisi ◽

S. Alobaidly

Keyword(s):

Parenteral Nutrition ◽

Preterm Infants ◽

Antibiotic Treatment ◽

Gestational Age ◽

Late Onset ◽

Blood Cultures ◽

Hospital Death ◽

Late Onset Sepsis ◽

Empiric Antibiotic ◽

Antibiotic Courses

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

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Implementing Potentially Better Practices to Improve Neonatal Outcomes After Reducing Postnatal Dexamethasone Use in Infants Born Between 501 and 1250 Grams

PEDIATRICS ◽

10.1542/peds.111.se1.e534 ◽

2003 ◽

Vol 111 (Supplement_E1) ◽

pp. e534-e541

Author(s):

Joseph W. Kaempf ◽

Betty Campbell ◽

Ronald S. Sklar ◽

Cindy Arduza ◽

Robert Gallegos ◽

...

Keyword(s):

Mechanical Ventilation ◽

Intensive Care ◽

Mortality Rate ◽

Length Of Stay ◽

Clinical Outcomes ◽

Airway Pressure ◽

Neonatal Intensive Care ◽

Positive Airway Pressure ◽

Late Onset ◽

Late Onset Sepsis

Objective. The purpose of this article is to describe how a neonatal intensive care unit (NICU) was able to reduce substantially the use of postnatal dexamethasone in infants born between 501 and 1250 g while at the same time implementing a group of potentially petter practices (PBPs) in an attempt to decrease the incidence and severity of chronic lung disease (CLD). Methods. This study was both a retrospective chart review and an ongoing multicenter evidence-based investigation associated with the Vermont Oxford Network Neonatal Intensive Care Quality Improvement Collaborative (NIC/Q 2000). The NICU specifically made the reduction of CLD and dexamethasone use a priority and thus formulated a list of PBPs that could improve clinical outcomes across 3 time periods: era 1, standard NICU care that antedated the quality improvement project; era 2, gradual implementation of the PBPs; and era 3, full implementation of the PBPs. All infants who had a birth weight between 501 and 1250 g and were admitted to the NICU during the 3 study eras were included (era 1, n = 134; era 2, n = 73; era 3, n = 83). As part of the NIC/Q 2000 process, the NICU implemented 3 primary PBPs to improve clinical outcomes related to pulmonary disease: 1) gentle, low tidal volume resuscitation and ventilation, permissive hypercarbia, increased use of nasal continuous positive airway pressure; 2) decreased use of postnatal dexamethasone; and 3) vitamin A administration. The total dexamethasone use, the incidence of CLD, and the mortality rate were the primary outcomes of interest. Secondary outcomes included the severity of CLD, total ventilator and nasal continuous positive airway pressure days, grades 3 and 4 intracranial hemorrhage, periventricular leukomalacia, stages 3 and 4 retinopathy of prematurity, necrotizing enterocolitis, pneumothorax, length of stay, late-onset sepsis, and pneumonia. Results. The percentage of infants who received dexamethasone during their NICU admission decreased from 49% in era 1 to 22% in era 3. Of those who received dexamethasone, the median number of days of exposure dropped from 23.0 in era 1 to 6.5 in era 3. The median total NICU exposure to dexamethasone in infants who received at least 1 dose declined from 3.5 mg/kg in era 1 to 0.9 mg/kg in era 3. The overall amount of dexamethasone administered per total patient population decreased 85% from era 1 to era 3. CLD was seen in 22% of infants in era 1 and 28% in era 3, a nonsignificant increase. The severity of CLD did not significantly change across the 3 eras, neither did the mortality rate. We observed a significant reduction in the use of mechanical ventilation as well as a decline in the incidence of late-onset sepsis and pneumonia, with no other significant change in morbidities or length of stay. Conclusions. Postnatal dexamethasone use in premature infants born between 501 and 1250 g can be sharply curtailed without a significant worsening in a broad range of clinical outcomes. Although a modest, nonsignificant trend was observed toward a greater number of infants needing supplemental oxygen at 36 weeks’ postmenstrual age, the severity of CLD did not increase, the mortality rate did not rise, length of stay did not increase, and other benefits such as decreased use of mechanical ventilation and fewer episodes of nosocomial infection were documented.

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Oropharyngeal Administration of Colostrum for Preventing Necrotizing Enterocolitis and Late-onset Sepsis in Preterm Infants with Gestational Age ≤ 32 Weeks: A Single-center Randomized Controlled Trial

10.21203/rs.3.rs-145820/v1 ◽

2021 ◽

Author(s):

xia ouyang ◽

changyi yang ◽

wenlong xiu ◽

yanhua hu ◽

susu mei ◽

...

Keyword(s):

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Enteral Feeding ◽

Gestational Age ◽

Late Onset ◽

Controlled Trial ◽

Control Group ◽

Clinical Trial Registry ◽

Late Onset Sepsis ◽

Full Enteral Feeding

Abstract BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) and improve short-term outcomes.ObjectiveTo evaluate the role of OAC in the early prevention of NEC and LOS in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA randomized, placebo-controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China. Preterm infants with GA ≤ 32 weeks were divided randomly into an OAC group, which received 0.4 ml maternal colostrum smearing via the oropharyngeal route every 3 hours for 10 days beginning within the first 48 hours after birth, and a control group, which received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 patients in the OAC group and 125 patients in the control group were finally enrolled. The incidence of NEC (Bell stage 2 or 3) and LOS was lower in the OAC group [2.4% vs. 10.4%, χ2 = 6.845, ༰=0.009; 4.7% vs. 13.6%, χ2 = 5.983, ༰=0.014]. In addition, the incidence of intraventricular hemorrhage (IVH) (stage 3 or 4) was lower [1.6% vs. 7.2%,χ2 = 4.775, ༰=0.029], and the time of achieving full enteral feeding was shorter [ 22.0 days vs. 25.0 days༌Z = 6༌424.500༌P = 0.009)] in the OAC group. No cases of adverse reactions were observed in either group.ConclusionsOAC is a safe and simple NICU procedure that yields a potential advantage in decreasing the incidence of NEC, LOS, and severe IVH and shortening the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry, ChiCTR1900023697, Registered 8 June 2019, Retrospectively registered, http://www.chictr.org.cn/edit.aspx? pid = 39398

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Evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0136 ◽

2020 ◽

Cited By ~ 1

Author(s):

Mohan Pammi ◽

Geoffrey A. Preidis ◽

William O Tarnow-mordi

Keyword(s):

Randomized Controlled Trials ◽

Late Onset ◽

Meta Analysis ◽

Current Evidence ◽

Preterm Neonates ◽

Controlled Trials ◽

Randomized Controlled ◽

Late Onset Sepsis ◽

Statistical Heterogeneity ◽

Tract Infections

In this commentary, we summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates. Our recently completed systematic review includes 12 randomized controlled trials performed all over the world. Our meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections. There were no adverse effects. There was no statistically significant decrease in necrotizing enterocolitis, mortality or neurodevelopmental impairment in lactoferrin supplemented preterm infants. There was significant statistical heterogeneity in the effects of lactoferrin on late-onset sepsis between larger and smaller studies, which may reflect either small study biases, differences in the effectiveness, dose or duration of supplemental lactoferrin products, or differences in underlying population risk, or any or all of these.

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Postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia in preterm infants

Paediatrics & Child Health ◽

10.1093/pch/pxaa073 ◽

2020 ◽

Vol 25 (5) ◽

pp. 322-326

Author(s):

Brigitte Lemyre ◽

Michael Dunn ◽

Bernard Thebaud

Keyword(s):

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Inhaled Corticosteroids ◽

Current Evidence ◽

Safe Alternative ◽

Risk Of Mortality ◽

Short Course ◽

Increased Risk ◽

Dexamethasone Therapy ◽

Physiological Dose

Abstract Historically, postnatal corticosteroids have been used to prevent and treat bronchopulmonary dysplasia (BPD), a significant cause of morbidity and mortality in preterm infants. Administering dexamethasone to prevent BPD in the first 7 days post-birth has been associated with increasing risk for cerebral palsy, while early inhaled corticosteroids appear to be associated with an increased risk of mortality. Neither medication is presently recommended to prevent BPD. New evidence suggests that prophylactic hydrocortisone, when initiated in the first 48 hours post-birth, at a physiological dose, and in the absence of indomethacin, improves survival without BPD, with no adverse neurodevelopmental effects at 2 years. This therapy may be considered by clinicians for infants at highest risk for BPD. Routine dexamethasone therapy for all ventilator-dependent infants is not recommended, but after the first week post-birth, clinicians may consider a short course of low-dose dexamethasone (0.15 mg/kg/day to 0.2 mg/kg/day) for individual infants at high risk for, or with evolving, BPD. There is no evidence that hydrocortisone is an effective or safe alternative to dexamethasone for treating evolving or established BPD. Current evidence does not support inhaled corticosteroids for the treatment of BPD.

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Improved weight attainment of extremely low-gestational-age infants with bronchopulmonary dysplasia

Journal of Perinatology ◽

10.1038/jp.2009.142 ◽

2009 ◽

Vol 30 (2) ◽

pp. 103-111 ◽

Cited By ~ 13

Author(s):

J Madden ◽

K Kobaly ◽

N M Minich ◽

M Schluchter ◽

D Wilson-Costello ◽

...

Keyword(s):

Bronchopulmonary Dysplasia ◽

Gestational Age ◽

Extremely Low Gestational Age

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Late-Onset Sepsis as a Risk Factor for Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants: A Nationwide Cohort Study

Scientific Reports ◽

10.1038/s41598-019-51617-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Euiseok Jung ◽

Byong Sop Lee

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Birth Weight ◽

Low Birth Weight ◽

Bronchopulmonary Dysplasia ◽

Late Onset ◽

Extremely Low Birth Weight ◽

Late Onset Sepsis ◽

The Impact ◽

Multiple Episodes

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.

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Risk Factors of Metabolic Bone Disease in Bronchopulmonary Dysplasia Premature Infants With Gestational Age Less Than 32 Weeks

10.21203/rs.3.rs-89304/v1 ◽

2020 ◽

Author(s):

Wenwen Chen ◽

Zhenghai Zhang ◽

Shuzhen Dai ◽

Xu Liping

Keyword(s):

Risk Factors ◽

Birth Weight ◽

Fetal Growth ◽

Gestational Age ◽

Bone Disease ◽

Fetal Growth Restriction ◽

Late Onset ◽

Significant Risk ◽

Extremely Low Birth Weight ◽

Late Onset Sepsis

Abstract BackgroundMetabolic bone disease (MBD) is a complication of multifactorial aetiology in preterm infants. Several risk factors have been identified in general. Bronchopulmonary Dysplasia (BPD) infants present an increased incidence of MBD, but it is unknown which factors contribute to this. The aim of this study was to determine the risk factors for developing MBD in BPD infants.MethodsA retrospective review of the medical records of BPD infants admitted to the Neonatal Intensive Care Unit (NICU) at Zhangzhou Hospital between Jun 2016 and May 2020. BPD infants with MBD were identified, two contemporaneous without MBD matched by gestational age and gender were randomly selected as control infants for each case of MBD. The association between putative risk factors and MBD was estimated with ORs and 95% CIs. A P-value threshold ≤0.2 was used in univariate analysis for inclusion into a multivariate (adjusted) model with a P-value of < 0.05 as statistically significant.ResultsA total of 156 BPD infants were enrolled with 52 cases of MBD and 104 controls. Fetal growth restriction (OR 5.60, 95% CI, 1.77–17.72), extremely low birth weight (OR 3.70, 95% CI, 1.35–10.10), feeding volume ＜80 mL/kg/day at the end of the 4th week after birth (OR 12.21, 95% CI, 3.89–38.33), cholestasis (OR 4.29, 95% CI, 1.65–11.15), and late onset sepsis (OR 3.79, 95% CI, 1.12–12.77) were found to be statistically significant risk factors for MBD in BPD infants.ConclusionIn gestational age homogeneous BPD infants, fetal growth restriction, extremely low birth weight, feeding volume＜80 mL/kg/day at the end of the 4th week after birth and late onset sepsis are significant risk factors for MBD. These findings provide potential predictive factors for MBD in BPD infants but still warrant prospective validation.

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