Risk Of Bronchopulmonary Dysplasia Research Articles

Human Milk Feeding Is Associated with Decreased Incidence of Moderate-Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants.

An increased rate of bronchopulmonary dysplasia (BPD) is reported in extremely preterm infants. A potential role of human milk feeding in protecting against this condition has been suggested. A retrospective descriptive study was conducted based on data about morbidity in the population of infants born between 22+0 and 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and discharged alive. The primary outcome was moderate-severe BPD. Associated conditions were studied, including human milk feeding at discharge. The temporal trends of BPD and human milk feeding rates at discharge were also studied. In the study population of 4341 infants, the rate of moderate-severe BPD was 43.7% and it increased to >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were birth weight, male sex, high-frequency oscillatory ventilation, duration of invasive mechanical ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901 and OR 0.714, 95% CI 0.602-0.847, respectively). During the study period, the proportion of infants with moderate-severe BPD fed any amount of human milk at discharge increased more than twofold. And the proportion of infants with moderate-severe BPD who were exclusively fed human milk at discharge increased at the same rate. Our work shows an inverse relationship between human milk feeding at discharge from the neonatal unit and the occurrence of BPD.

The impact of small-for-gestational-age Status on the outcomes in very-Low-birth-weight (VLBW) premature infants: a prospective cohort study in Taiwan.

The impact of small-for-gestational-age (SGA) on very-low-birth-weight (VLBW) premature infants remains inconclusive. This study aimed to assess the effects of being born SGA status on the short-term and long-term outcomes in VLBW preterm infants. We conducted a population-based, prospective cohort study on VLBW preterm infants born in Taiwan between 2012 and 2017. Sociodemographic, neonatal, growth and neurological data at 2 years of corrected age were collected. A total of 4243 VLBW infants born at 24 through 32 completed weeks' gestation participated in this study, of whom 1,005 had SGA status defined as a birth weight <10th percentile of gestation, and 3,238 did not (the non-SGA group).We compared the risks of short-term outcomes (neonatal mortality and morbidities), long-term outcomes (growth status, including weight, height, and head circumference <10th percentile, and neurodevelopmental impairments at 2 years of age). Subgroup analysis was performed by stratification of gestation age (GA): GA 24-26, 27-29 and 30-32 weeks. In the analysis of short-term outcomes, the SGA group had an increased risk of neonatal mortality [adjusted odds ratio (OR) = 2.66, 2.99, and 2.19, respectively] in all GA subgroups in comparison with the non-SGA group (p < 0.05). The SGA group had a significantly increased risk of bronchopulmonary dysplasia in GA 27-29 and 30-32 weeks (adjusted OR = 2.11 and 1.86, respectively). We also found that there was an increased risk of severe retinopathy of prematurity in GA 24-26 and 27-29 weeks in the SGA group compared with the non-SGA group (adjusted OR = 1.68 and 1.59, respectively).In the analysis of long-term outcomes, the SGA group had a significantly increased risk of NDI throughout all GA subgroups (adjusted = 1.94, 1.33, and 1.35, respectively) in comparison with the non-SGA group. The SGA groups also had an increased risk of growth status <10th percentile at 2 years of age (p < 0.05). SGA VLBW premature infants had higher risks of neonatal death, growth status <10th percentile, and NDI at 2 years of corrected age compared with the non- SGA premature infants. Prenatal surveillance, postnatal attention, and long- term follow-up are warranted to improve the outcomes of VLBW SGA premature infants.

Enteral supplementation with high-dose docosahexaenoic acid on the risk of bronchopulmonary dysplasia in very preterm infants: a collaborative study protocol for an individual participant data meta-analysis

IntroductionSevere bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA)...

Relationship between hematological parameters and bronchopulmonary dysplasia in premature infants

Objective To evaluate the association between hematological parameters on the first day of life and bronchopulmonary dysplasia (BPD) in preterm infants. Methods This retrospective study involved all premature infants admitted to our neonatal intensive care unit from January 2017 to June 2022. BPD was diagnosed based on hypoxia exposure for ≥28 days. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet count (PLT), mean platelet volume (MPV), and platelet mass index (PMI) were compared between infants with and without BPD. Multivariate analysis was conducted to evaluate the association between hematological parameters and BPD. Results This study involved 124 premature infants (48 with BPD, 76 without BPD). The BPD group had a lower gestational age and lower weight. The NLR, MPV, and PLR were considerably higher and the PLT and MPI were lower in the BPD than non-BPD group. After adjusting for covariates, logistic regression analysis suggested that the NLR, PLT, and PMI were independent risk factors for BPD. Moreover, the receiver operating characteristic curve indicated that the NLR, PLT, and PMI were reliable predictors of BPD. Conclusion Our findings suggest that a higher NLR and a lower PLT and PMI on the first day may increase the risk of BPD.

Association of Ureaplasma infection pattern and azithromycin treatment effect with bronchopulmonary dysplasia in Ureaplasma positive infants: a cohort study

BackgroundIt is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD).MethodsA retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment.ResultsA total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000–0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548–6.147).ConclusionEffective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.

L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.

Prenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD. We hypothesize that L-CIT will attenuate lipopolysaccharide (LPS)-induced inflammation and oxidative stress in our rat model of neonatal lung injury. Newborn rats during the saccular stage of lung development were used to investigate the effect of L-CIT on LPS-induced lung histopathology and pathways involved in inflammatory, antioxidativeprocesses, and mitochondrial biogenesis in lungs in vivo, and in primary culture of pulmonary artery smooth muscle cells, in vitro. L-CIT protected the newborn rat lung from LPS-induced: lung histopathology, ROS production, NFκB nuclear translocation, and upregulation of gene and protein expression of inflammatory cytokines (IL-1β, IL-8, MCP-1α, and TNF-α). L-CIT maintained mitochondrial morphology, increased protein levels of PGC-1α, NRF1, and TFAM (transcription factors involved in mitochondrial biogenesis), and induced SIRT1, SIRT3, and superoxide dismutases protein expression. L-CIT may be efficacious in decreasing early lung inflammation and oxidative stress mitigating progression to BPD. The nonessential amino acid L-citrulline (L-CIT) mitigated lipopolysaccharide (LPS)-induced lung injury in the early stage of lung development in the newborn rat. This is the first study describing the effect of L-CIT on the signaling pathways operative in bronchopulmonary dysplasia (BPD) in a preclinical inflammatory model of newborn lung injury. If our findings translate to premature infants, L-CIT could decrease inflammation, oxidative stress and preserve mitochondrial health in the lung of premature infants at risk for BPD.

Oxygen and mechanical stretch in the developing lung: risk factors for neonatal and pediatric lung disease.

Chronic airway diseases, such as wheezing and asthma, remain significant sources of morbidity and mortality in the pediatric population. This is especially true for preterm infants who are impacted both by immature pulmonary development as well as disproportionate exposure to perinatal insults that may increase the risk of developing airway disease. Chronic pediatric airway disease is characterized by alterations in airway structure (remodeling) and function (increased airway hyperresponsiveness), similar to adult asthma. One of the most common perinatal risk factors for development of airway disease is respiratory support in the form of supplemental oxygen, mechanical ventilation, and/or CPAP. While clinical practice currently seeks to minimize oxygen exposure to decrease the risk of bronchopulmonary dysplasia (BPD), there is mounting evidence that lower levels of oxygen may carry risk for development of chronic airway, rather than alveolar disease. In addition, stretch exposure due to mechanical ventilation or CPAP may also play a role in development of chronic airway disease. Here, we summarize the current knowledge of the impact of perinatal oxygen and mechanical respiratory support on the development of chronic pediatric lung disease, with particular focus on pediatric airway disease. We further highlight mechanisms that could be explored as potential targets for novel therapies in the pediatric population.

Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm

High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ. To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit. This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023. Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home. Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable. Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points). This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.

Association between the development of bronchopulmonary dysplasia and platelet transfusion: a protocol for a systematic review and meta-analysis.

There is a lack of consensus on the management of thrombocytopenia in preterm infants, and the threshold for prophylactic platelet transfusion varies widely among clinicians and institutions. Reports in animal models suggested that platelets may play a relevant role in lung alveolarization and regeneration. Bronchopulmonary dysplasia (BPD) is a severe respiratory condition with a multifactorial origin that affects infants born at the early stages of lung development. Recent randomized controlled trials on the platelets count threshold for prophylactic transfusions in preterm infants with thrombocytopenia suggest that a higher exposition to platelet transfusion may increase the risk of BPD. Here, we report a protocol for a systematic review, which aims to assist evidence-based clinical practice and clarify if the administration of platelet products may be associated with the incidence of BPD and/or death in preterm infants. MEDLINE, Embase, Cochrane databases, and sources of gray literature for conference abstracts and trial registrations will be searched with no time or language restrictions. Case-control studies, cohort studies, and nonrandomized or randomized trials that evaluated the risk for BPD and/or death in preterm infants exposed to platelet transfusion will be included. Data from studies that are sufficiently similar will be pooled as appropriate. Data extraction forms will be developed a priori. Observational studies and nonrandomized and randomized clinical trials will be analyzed separately. Odds ratio with 95% confidence interval (CI) for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes will be combined. The expected heterogeneity will be accounted for using a random-effects model. Subgroup analysis will be performed based on a priori-determined covariate of interest. In case of sufficient homogeneity of interventions and outcomes evaluated, results from subgroups of studies will be pooled together in a meta-analysis. This systematic review will investigate the association of BPD/death with platelet components administration in preterm infants, and, consequently, it will provide reliable indications for the evidence-based management of premature patients with thrombocytopenia.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial

Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. Infants were randomized to 10 days of hydrocortisone or placebo treatment. Infants' baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. ClinicalTrials.gov Identifier: NCT01353313.

Late-Onset Sepsis in Very Low Birth Weight Premature Infants: A 10-Year Review of a Brazilian Tertiary University Hospital-the Challenge Remains.

This study aimed to assess the incidence of late-onset sepsis (LOS), associated risk factors, and short-term prognosis in very low birth weight (VLBW) infants in a 10-year period. A cohort study was conducted with 752 VLBW preterm infants-23 to 33 gestational weeks and 400 to 1,500 g birth weight-admitted to a neonatal intensive care unit from 2008 to 2017 and who survived over 72 hours. LOS was defined as clinical and laboratory signs of infection, whether or not confirmed by blood culture. VLBW infants were divided into groups and compared: no LOS versus proven LOS versus clinical LOS. Study variables included maternal, birth, and neonatal data, morbidities, procedures, etiological agents, and outcome-death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage, and retinopathy of prematurity (ROP). Analysis of variance with multiple Tukey's or Wald's comparison with gamma distribution, and stepwise multiple logistic regression model, adjusted for year, and gestational age, were used for statistical analysis. LOS incidence was 39% (proven LOS: 29%; clinical LOS: 10%). Septic VLBW infants showed higher mortality (proven LOS: 23.2%; clinical LOS: 41.9%) compared with no LOS (8.9%). Coagulase-negative staphylococci (56%), Gram-negative (26%), and fungi (8%) were the most frequent etiological agents. In comparing the groups, septic VLBW infants had lower gestational age and birth weight, presented more morbidities, and underwent more invasive procedures. The risk factors for proven and clinical LOS were days of mechanical ventilation and parenteral nutrition. LOS was associated with increased risk of death, BPD, and ROP. LOS showed high incidence and mortality, often caused by Gram-positive bacteria. Care interventions were the main risk factors associated. LOS had a major negative impact on short-term prognosis in VLBW infants. LOS reduction strategies are necessary and urgent. · LOS is associated with clinically significant neonatal morbidities and death in VLBW premature infants.. · There is association between LOS and duration of intensive care interventions.. · Quality improvement initiatives can be a pathway for LOS reduction..

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants

Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants. This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age. A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis

BackgroundSepsis is one of the most important complications in preterm infants. For this reason, many such infants receive antibiotics during their hospital stay. However, early antibiotic therapy has also been...

Dose pulmonary hemorrhage increase the risk of bronchopulmonary dysplasia in very low birth weight infants?

Objective To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). Methods The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). Results By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581–5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736–7.834). Conclusion It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.

Surfactant delivery via thin catheter in preterm infants: A systematic review and meta-analysis.

Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants <29 weeks' gestation and the neurodevelopmental outcomes remain unclear. Thus, our objective was to systematically review and meta-analyze the efficacy and safety of STC compared to intubation for surfactant or nasal continuous positive airway pressure (nCPAP) in preterm infants with RDS. Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE. Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate). Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation.

Pulmonary Vascular Phenotypes of Prematurity: The Path to Precision Medicine

Pulmonary hypertension (PH) is associated with significant morbidities and high mortality in preterm infants, yet mechanisms contributing to the pathogenesis of PH, the impact of early pulmonary vascular disease (PVD) on the risk for BPD, the role for PH-targeted drug therapies, and long-term pulmonary vascular sequelae remain poorly understood. PVD is not a homogeneous disease, rather, PVD in the setting of prematurity includes various phenotypes as based on underlying pathophysiology, the severity of associated PH, the timing of disease onset, its contribution to hemodynamic and respiratory status, late outcomes, and other features. As with term newborns, severe hypoxemia with acute respiratory failure (HRF) in preterm infants can be due to marked elevation of pulmonary artery pressure with extrapulmonary shunt, traditionally referred to as persistent pulmonary hypertension of the newborn (PPHN). Transient and less severe levels of PH can also be observed during the early transition after birth without evidence of severe HRF, representing physiologic PH or delayed pulmonary vascular transition in preterm infants. Importantly, echocardiographic evidence of early PH has been strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), late PH, and chronic respiratory disease during infancy and early childhood. Late PH beyond the first postnatal months in preterm in neonates with established BPD is further associated with poor outcomes, especially as related to BPD severity. In addition, echocardiographic signs of PVD can further persist throughout childhood and may lead to chronic PH of variable severity and cardiac maldevelopment in prematurely born young adults. This review discusses the importance of characterizing diverse pulmonary vascular phenotypes in preterm infants to better guide clinical care and research, and to enhance the development of more precise therapeutic strategies to optimize early and late outcomes of preterm infants.

Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections.

To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015-2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity.

Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity.

A Quality Improvement Project to Reduce Antibiotic Exposure in Premature Neonates.

Overuse of antibiotics in NICUs is a problem worldwide. Unnecessary antibiotic exposure leads to resistance, changes in the microbiome, and increases the risk of bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis (LOS), and mortality in neonates. We aimed to safely reduce the antibiotic usage rate (AUR) in our level IV unit by 10% by December 2018. A multidisciplinary quality improvement project took place as part of a Vermont Oxford Network initiative in 2018. Multiple interventions took place, including identification of variations in practices and subsequent standardization through the creation of early onset and LOS guidelines, mass education, improved visibility of the guidelines, and standardized documentation. The main outcome measure for this project was the AUR for infants born <35 weeks' gestation expressed as antibiotic doses per 1000 patient days. The AUR decreased from a mean of 524 to 394, for a decrease of 24.8%. Results have been sustained for 3 years. Main contributors that led to the sustained success include decreasing the overall use of antibiotics for early onset sepsis, as well as the duration when cultures are negative. The number of LOS courses also decreased slightly. We noted no cases of inadequately treated sepsis resulting in subsequent positive cultures. Creation of guidelines with mass education and ongoing feedback/monitoring can result in a safe reduction of AUR in the NICU.