OBJECTIVETo explore the clinical efficacy of intratracheal instillation of pulmonary surfactant (PS) combined with budesonide for preventing bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants.

METHODSThirty VLBW infants with gestational age <32 weeks who developed neonatal respiratory distress syndrome (NRDS) (grade III-IV) suffering from intrauterine infection were randomly assigned into a PS + budesonide group and a PS alone group. The changes were compared between the two groups in arterial blood gas indexes, oxygenation index (OI), duration of mechanical ventilation, duration of oxygen supplementation, incidence of BPD, mortality rate at 36 weeks corrected gestational age and incidences of other complications except BPD.

RESULTSCompared with the PS alone group, the PS+budesonide group had a lower incidence of BPD, shorter duration of mechanical ventilation and oxygen supplementation (P<0.05). On the 2nd to 6th day after treatment, the PS+budesonide group had higher pH value of arterial blood gas and OI and lower carbon dioxide partial pressure compared with the PS alone group (P<0.05). There were no significant differences in the mortality rate at 36 weeks corrected gestational age and the incidences of other complications except BPD between the two groups (P>0.05).

CONCLUSIONSIntratracheal instillation of PS combined with budesonide can effectively reduce the incidence of BPD in VLBW premature infants with severe NRDS.

Bronchopulmonary Dysplasia ; prevention & control ; Budesonide ; administration & dosage ; Female ; Humans ; Infant, Newborn ; Infant, Very Low Birth Weight ; Male ; Pulmonary Surfactants ; administration & dosage ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; drug therapy

OBJECTIVETo study the efficacy of different preparations of budesonide combined with pulmonary surfactant (PS) in improving blood gas levels and preventing bronchopulmonary dysplasia (BPD) in preterm infants with neonatal respiratory distress syndrome (NRDS).

METHODSA total of 184 preterm infants who developed NRDS within 4 hours after birth were randomly administered with PS + continuous inhalation of budesonide aerosol (continuous aerosol group), PS+budesonide solution (solution group), PS + single inhalation of budesonide aerosol (single aerosol group), and PS alone, with 46 neonates in each group. The changes in arterial blood gas levels, rate of invasive mechanical ventilation after treatment, time of assisted ventilation, rate of repeated use of PS, and the incidence of BPD were compared between the four groups.

RESULTSOn the 2nd to 4th day after treatment, pH, PCO2, and oxygenation index (FiO2/PaO2) showed significant differences among the four groups, and the continuous aerosol group showed the most improvements of all indicators, followed by the solution group, single aerosol group, and PS alone group. The continuous aerosol group had a significantly shorter time of assisted ventilation than the other three groups (P<0.05). The solution group had a significantly shorter time of assisted ventilation than the single aerosol and PS alone groups (P<0.05). The rate of invasive mechanical ventilation after treatment, rate of repeated use of PS, and incidence of BPD showed significant differences among the four groups (P<0.05), and the continuous aerosol group had the lowest rates, followed by the solution group.

CONCLUSIONSA combination of PS and continuous inhalation of budesonide aerosol has a better efficacy in the treatment of NRDS than a combination of PS and budesonide solution. The difference in reducing the incidence of BDP between the two administration methods awaits further investigation with a larger sample size.

Bronchopulmonary Dysplasia ; prevention & control ; Budesonide ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactants ; administration & dosage ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; drug therapy

The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (> or =3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.
Apnea/*drug therapy ; Bronchopulmonary Dysplasia/drug therapy ; Caffeine/*administration & dosage/adverse effects ; Citrates/*administration & dosage/adverse effects ; Enterocolitis, Necrotizing/etiology ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Very Low Birth Weight ; Risk Factors ; Treatment Outcome

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants < 34 weeks gestational age (GA) within 1 yr following discharge from the neonatal intensive care unit (NICU). Infants (n = 1,140) who were born and admitted to the NICUs of 46 hospitals in Korea from April to September 2012, and followed up for > 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) +/- 2(+5) weeks and 1,502 +/- 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.
Antiviral Agents/therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy/pathology ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Male ; Odds Ratio ; Palivizumab/therapeutic use ; Patient Discharge ; Patient Readmission ; Republic of Korea ; Respiratory Syncytial Virus Infections/drug therapy/*pathology/virology ; Respiratory Syncytial Viruses/*isolation & purification ; Risk Factors ; Siblings

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.
Animals ; Bronchopulmonary Dysplasia/*drug therapy/*metabolism/pathology ; Deferoxamine/*administration & dosage ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Male ; Pulmonary Alveoli/drug effects/*growth & development/metabolism/pathology ; Pulmonary Veins/drug effects/*growth & development/pathology ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Up-Regulation/drug effects

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.
Biological Products/administration & dosage/*therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Phospholipids/administration & dosage/*therapeutic use ; Pulmonary Surfactants/administration & dosage/*therapeutic use ; Republic of Korea ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn/*drug therapy ; Retrospective Studies ; Risk ; Treatment Outcome ; Ventilator Weaning

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.
Biological Products/administration & dosage/*therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Phospholipids/administration & dosage/*therapeutic use ; Pulmonary Surfactants/administration & dosage/*therapeutic use ; Republic of Korea ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn/*drug therapy ; Retrospective Studies ; Risk ; Treatment Outcome ; Ventilator Weaning

The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1+/-1.7 weeks, and the mean birth weight was 889.4+/-222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0+/-5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency.
Antibiotic Prophylaxis/*methods ; Antiviral Agents/*therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/*complications ; Female ; Gestational Age ; Hospitalization/statistics & numerical data ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; *Infant, Very Low Birth Weight ; Length of Stay ; Male ; Palivizumab/*therapeutic use ; Prospective Studies ; Respiratory Syncytial Virus Infections/drug therapy/*epidemiology/prevention & control ; Respiratory Syncytial Viruses/drug effects ; Risk ; Risk Factors

OBJECTIVETo investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants.

METHODSSixty premature infants (gestational age ≤ 34 weeks) with HRF were randomized into NO and control groups between 2012 and 2013, with 30 cases in each group. Both groups received nasal continuous positive airway pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at least 7 days or until weaning in the NO group. The general conditions, blood gas results, complications, and clinical outcomes of the two groups were analyzed.

RESULTSThe NO group showed significantly more improvement in blood gas results than the control group after 12 hours of treatment (P<0.05). After that, the change in oxygenation status over time showed no significant difference between the two groups (P>0.05). There were no significant differences in total time of assisted ventilation and duration of oxygen therapy between the two groups (P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and pneumothorax in infants showed no significant differences between the NO and control groups (P>0.05), but the incidence of IVH and mortality were significantly lower in the NO group than in the control group (7% vs 17%, P<0.05; 3% vs 13%, P<0.05).

CONCLUSIONSNO inhalation may improve oxygenation status and reduce the mortality in premature infants with HRF, but it cannot reduce the incidence of BPD and the total time of mechanical ventilation or nCPAP and duration of oxygen therapy. NO therapy may have a brain-protective effect for premature infants with HRF and does not increase clinical complications.

Administration, Inhalation ; Blood Gas Analysis ; Bronchopulmonary Dysplasia ; epidemiology ; Humans ; Hypoxia ; complications ; Incidence ; Infant, Newborn ; Infant, Premature ; Nitric Oxide ; administration & dosage ; Respiratory Insufficiency ; blood ; complications ; drug therapy

PURPOSE: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-gamma agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. RESULTS: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. CONCLUSION: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.
Animals ; Bronchopulmonary Dysplasia/*drug therapy ; Female ; Hypertension, Pulmonary/drug therapy ; Immunohistochemistry ; Lung/drug effects/pathology ; PPAR gamma/*agonists ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones/*therapeutic use ; Vasodilator Agents/*therapeutic use