Severe Neonatal Respiratory Distress Syndrome Research Articles

Prospective, non-blinded, randomized controlled trial on early administration of pulmonary surfactant guided by lung ultrasound scores in very preterm infants: study protocol.

Bedside lung ultrasonography has been widely used in neonatal intensive care units (NICUs). Lung ultrasound scores (LUS) may predict the need for pulmonary surfactant (PS) application. PS replacement therapy is the key intervention for managing moderate to severe neonatal respiratory distress syndrome (NRDS), with early PS administration playing a positive role in improving patient outcomes. Lung ultrasonography aids in the prompt diagnosis of NRDS, while LUS offers a semi-quantitative assessment of lung health. However, the specific methodologies for utilizing LUS in clinical practice remain controversial. This study hypothesizes that, in very preterm infants [<32 weeks gestational age (GA)] exhibiting respiratory distress symptoms, determining PS application through early postnatal LUS combined with clinical indicators, as opposed to relying solely on clinical signs and chest x-rays, can lead to more timely PS administration, reduce mechanical ventilation duration, improve patient outcomes, and lower the occurrence of bronchopulmonary dysplasia (BPD). This is a protocol for a prospective, non-blinded, randomized controlled trial that will be conducted in the NICU of a hospital in China. Eligible participants will include very preterm infants (< 32 weeks GA) exhibiting signs of respiratory distress. Infants will be randomly assigned in a 1:1 ratio to either the ultrasound or control group. In the ultrasonography group, the decision regarding PS administration will be based on a combination of lung ultrasonography and clinical manifestations, whereas in the control group, it will be determined solely by clinical signs and chest x-rays. The primary outcome measure will be the mechanical ventilation duration. Statistical analysis will employ independent sample t-tests with a significance level set at α = 0.05 and a power of 80%. The study requires 30 infants per group (in total 60 infants). This study aims to demonstrate that determining PS application based on a combination of LUS and clinical indicators is superior to traditional approaches. This approach may enhance the accuracy of NRDS diagnosis and facilitate early prediction of PS requirements, thereby reducing the duration of mechanical ventilation. The findings of this research may contribute valuable insights into the use of LUS to guide PS administration.

Diagnostic value of bedside lung ultrasound and 12-zone score in the 65 cases of neonatal respiratory distress syndrome and its severity

ObjectiveTo explore the predictive value of bedside lung ultrasound score in the severity of neonatal respiratory distress syndrome (NRDS) and mechanical ventilation and extubation.MethodsThe clinical data of 65 neonates with NRDS and invasive mechanical ventilation diagnosed in the neonatal intensive care unit of our hospital from July 2021 to July 2022 were retrospectively analyzed. 65 neonates were included in the NRDS group, and 40 neonates with other common lung diseases were selected as the other lung disease groups. All neonates underwent lung ultrasound and X-ray examination. The correlation between lung ultrasound scores and arterial blood gas indexes was analyzed by Pearson. The efficacy of successful evacuation of mechanical ventilation was evaluated by lung ultrasound analysis by ROC curve analysis.ResultsThe positive rates of lung consolidation and white lung in NRDS group were higher than the other lung disease groups (P < 0.05). The positive rates of bronchial inflation sign and double lung points were lower than these in the other lung disease groups (P < 0.05). The ultrasound scores of both lungs, left lung, right lung, bilateral lung and double basal lung in the NRDS group were significantly higher than those in the other lung disease groups (P < 0.05). There was a significant positive correlation between lung ultrasound score and X-ray grade (r = 0.841, P < 0.001). The area under the curve (AUC) of lung ultrasound score for the differential diagnosis of NRDS and common lung diseases was 0.907. The AUC of lung ultrasound score in the differential diagnosis of mild and moderate, and moderate and severe NRDS were 0.914 and 0.933, respectively, which had high clinical value. The lung ultrasound score was positively correlated with the level of PaCO2 (r = 0.254, P = 0.041), and negatively correlated with the levels of SpO2 and PaO2 (r = − 0.459, − 0.362, P = 0.001, 0.003). The AUC of successful mechanical ventilation withdrawal predicted by the pulmonary ultrasound score before extubation was 0.954 (95% CI 0.907–1.000). The predictive value of successful extubation was 10 points of the pulmonary ultrasound score, with a sensitivity of 93.33% and a specificity of 88.00%.ConclusionThe bedside lung ultrasound score can intuitively reflect the respiratory status of neonates, which provides clinicians with an important basis for disease evaluation.

Feasibility of ultrasound in the diagnosis of neonatal respiratory distress syndrome in preterm infants.

The aim of this study was to investigate the feasibility of lung ultrasound in the diagnosis of neonatal respiratory distress syndrome (NRDS) in preterm infants. One hundred and nine preterm infants were prospectively recruited. Three ultrasound diagnostic criteria were developed to diagnose preterm infants with NRDS: (A) thickened or not smooth pleural line, part of the lung field shows diffuse 'B-line' sign or alveolar-interstitial syndrome (AIS); (B) thickened or not smooth pleural line, all lung fields show AIS, signifying the 'white lung' sign; (C) thickened or rough pleural line, 'white lung' sign and 'lung consolidation' sign can be observed in any lung field. The sensitivity and negative predictive value of NRDS in preterm infants with diagnostic criteria A were 100%, but the specificity and positive predictive value were 67.95 and 55.36%, respectively. The specificity and positive predictive value of diagnostic criteria B and C were 100%, while the 95% CI of diagnostic criteria B was narrower than diagnostic criteria C. The sensitivity and negative predictive value of diagnostic criteria B were higher than that of diagnostic criteria C. Of the 31 NRDS cases, 15 cases had severe NRDS and the other 16 did not have severe NRDS. Thickened or rough pleural line with white lung sign is an important characteristic for the diagnosis of NRDS by lung ultrasound. White lung sign combined with the lung consolidation sign had high diagnostic efficacy when distinguishing severe NRDS from not severe NRDS.

Efficacy of volume-targeted ventilation versus high-frequency oscillatory ventilation in the treatment of neonatal respiratory distress syndrome

To study the clinical efficacy of volume-targeted ventilation (VTV) versus high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory distress syndrome (NRDS). A retrospective cohort analysis was performed on the medical data of 140 neonates with severe NRDS who were admitted from September 2016 to February 2022, with 55 neonates in the VTV group and 85 in the HFOV group. The neonates in the VTV group received conventional mechanical ventilation and target tidal volume, and those in the HFOV group received HFOV. Arterial blood gas parameters were collected at 48 hours after admission, and related indices during hospitalization were recorded, including mortality rate, duration of invasive mechanical ventilation, duration of oxygen therapy, and the incidence rates of complications. Compared with the VTV group, the HFOV group had significantly lower incidence rates of grade Ⅲ-Ⅳ periventricular-intraventricular hemorrhage and neonatal necrotizing enterocolitis (P<0.05), and there were no significant differences between the two groups in the duration of invasive mechanical ventilation, the duration of oxygen therapy, mortality rate, and the incidence rates of bronchopulmonary dysplasia, hypocapnia, hypercapnia, periventricular leukomalacia, and retinopathy of prematurity (P>0.05). HFOV has a better clinical efficacy than VTV in the treatment of NRDS.

Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency.

ABCA3 is a phospholipid transporter protein required for surfactant assembly in lamellar bodies of alveolar type II cells. Biallelic pathogenic ABCA3 variants cause severe neonatal respiratory distress syndrome or childhood interstitial lung disease. However, ABCA3 genotype alone does not explain the diversity in disease presentation, severity, and progression. Additionally, monoallelic ABCA3 variants have been reported in infants and children with ABCA3-deficient phenotypes. The effects of most ABCA3 variants identified in patients have not been characterized at the RNA level. ABCA3 allele-specific expression occurs in some cell types due to epigenetic regulation. We obtained lung tissue at transplant or autopsy from 16 infants and children with ABCA3 deficiency due to compound heterozygous ABCA3 variants for biologic characterization of the predicted effects of ABCA3 variants at the RNA level and determination of ABCA3 allele expression. We extracted DNA and RNA from frozen lung tissue and reverse-transcribed cDNA from mRNA. We performed Sanger sequencing to assess allele-specific expression by comparing the heights of variant nucleotide peaks in amplicons from genomic DNA and cDNA. We found similar genomic and cDNA variant nucleotide peak heights and no evidence of allele-specific expression among explant or autopsy samples with biallelic missense ABCA3 variants (n = 6). We observed allele-specific expression of missense alleles in trans with frameshift (n = 4) or nonsense (n = 1) variants, attributable to nonsense-mediated decay. The missense variant c.53 A > G;p.Gln18Arg, located near an exon-intron junction, encoded abnormal splicing with skipping of exon 4. Biologic characterization of ABCA3 variants can inform discovery of variant-specific disease mechanisms.

Gene Therapy Potential for Genetic Disorders of Surfactant Dysfunction.

Pulmonary surfactant is critically important to prevent atelectasis by lowering the surface tension of the alveolar lining liquid. While respiratory distress syndrome (RDS) is common in premature infants, severe RDS in term and late preterm infants suggests an underlying genetic etiology. Pathogenic variants in the genes encoding key components of pulmonary surfactant including surfactant protein B (SP-B, SFTPB gene), surfactant protein C (SP-C, SFTPC gene), and the ATP-Binding Cassette transporter A3 (ABCA3, ABCA3 gene) result in severe neonatal RDS or childhood interstitial lung disease (chILD). These proteins play essential roles in pulmonary surfactant biogenesis and are expressed in alveolar epithelial type II cells (AEC2), the progenitor cell of the alveolar epithelium. SP-B deficiency most commonly presents in the neonatal period with severe RDS and requires lung transplantation for survival. SFTPC mutations act in an autosomal dominant fashion and more commonly presents with chILD or idiopathic pulmonary fibrosis than neonatal RDS. ABCA3 deficiency often presents as neonatal RDS or chILD. Gene therapy is a promising option to treat monogenic lung diseases. Successes and challenges in developing gene therapies for genetic disorders of surfactant dysfunction include viral vector design and tropism for target cell types. In this review, we explore adeno-associated virus (AAV), lentiviral, and adenoviral (Ad)-based vectors as delivery vehicles. Both gene addition and gene editing strategies are compared to best design treatments for lung diseases resulting from pathogenic variants in the SFTPB, SFTPC, and ABCA3 genes.

Correlations of Serum 1,25-Hydroxy Vitamin D3 level with Severity and Prognosis of Neonatal Respiratory Distress Syndrome.

This study was done to explore the correlations of serum 1,25-hydroxy vitamin D3 [1,25-(OH)2-VitD3] level with severity and prognosis of neonatal respiratory distress syndrome (NRDS). The clinical data of 145 NRDS children admitted between April 2019 and June 2020 were retrospectively analyzed. The subjects were comprised of 76 boys and 69 girls. Based on NRDS severity, they were assigned into mild group (n = 82) and severe group (n = 63), and their general data were compared. The independent factors affecting NRDS severity were evaluated by multivariate logistic regression analysis. The correlations of serum 1,25-(OH)2-VitD3 level in NRDS children with NRDS severity and other related blood test indices were analyzed using Spearman's and Pearson's methods. On the basis of multivariate analysis results, a prediction model was established using R3.6.0 software, which was validated by the receiver operating characteristic (ROC) curve and consistency index. The association between serum 1,25-(OH)2-VitD3 level and prognosis was evaluated through Kaplan-Meier curve. The severe group had higher groups of children with a gestational age < 39 weeks, spontaneous delivery, selective cesarean section, intrauterine distress, intrauterine infection, maternal hypertension, maternal dyslipidemia, and older maternal age than the mild group (p < 0.05). Procalcitonin, C-reactive protein, activin-A, Clara cell protein-16, interleukin-18, and IL-10 were significantly higher in the severe group than those in the mild group (p < 0.05), while serum bicarbonate, 1,25-(OH)2-VitD3, vitamin A, and IL-8 were significantly lower in the severe group than those in the mild group (p < 0.05). Multivariate logistic regression analysis results exhibited that gestational age < 39 weeks, lower 1,25-(OH)2-VitD3 and vitamin A levels, higher activin-A and CC-16 were independent risk factors for severe NRDS (p < 0.05). ROC curve analysis revealed that the area under the ROC curve of the model was 0.785, and the prediction accuracy was 88.08%. Serum 1,25-(OH)2-VitD3 level was significantly negatively correlated with NRDS severity (r = -0.287, p < 0.001), activin-A (r = -0.073, p < 0.001), and CC-16 (r = -0.098, p < 0.001), but positively correlated with vitamin A (r = 0.009, p < 0.001). Kaplan-Meier curve revealed that the survival rate of NRDS children with a high 1,25-(OH)2-VitD3 level was significantly higher than that of children with a low 1,25-(OH)2-VitD3 level (p < 0.001). 1,25-(OH)2-VitD3 is an independent influencing factor for the severity of NRDS and may affect the prognosis of NRDS children.

Analysis of diagnosing neonatal respiratory distress syndrome with lung ultrasound score

Objectives:To investigate the diagnostic effect of lung ultrasound on neonatal respiratory distress syndrome (NRDS) and to analyze the clinical application value of pulmonary ultrasound score.Methods:Sixty-five NRDS babies who were diagnosed in our hospital from August 2019 to October 2020 were selected as the observation group, and 65 healthy babies were selected as the control group. Children in the two groups underwent lung ultrasound examination. The characteristic signs of lung ultrasound in the two groups were analyzed, and the detection rate of various signs and lung ultrasound score were compared between the two groups.Results:The main manifestations of lung ultrasound in NRDS children were pulmonary parenchyma, abnormal pleural line, blurred or disappeared A line, pleural effusion, white lung, and weak or disappeared pulmonary pulsation; the lung ultrasound scores of different positions in the observation group were higher than those in the control group, and the differences were statistically significant (P<0.05). The detection rates of signs such as lung parenchyma, abnormal pleural line, disappeared A line, diffuse pulmonary edema, and air bronchogram in the observation group were significantly higher than that in the control group (P<0.05), and there was no significant difference in the detection rate of the sign of B line existence between the two groups (P>0.05).Conclusion:Lung ultrasound has a high diagnostic value in diagnosing NRDS, and lung ultrasound score can evaluate the severity of NRDS in babies to further optimize the diagnosis results, which has important clinical significance.

Benefits of a Single Dose of Betamethasone in Imminent Preterm Labour.

Background: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. Materials and methods: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. Results: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07–0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01–0.8)) and maximum FiO2 (p = 0.01) was observed. Conclusions: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals.

Hydroxychloroquine, a successful treatment for lung disease\xa0in ABCA3 deficiency gene mutation: a case report

BackgroundPulmonary surfactant is a complex mixture of lipids and specific proteins that stabilizes the alveoli at the end of expiration. Mutations in the gene coding for the triphosphate binding cassette transporter A3 (ABCA3), which facilitates the transfer of lipids to lamellar bodies, constitute the most frequent genetic cause of severe neonatal respiratory distress syndrome and chronic interstitial lung disease in children. Hydroxychloroquine can be used as an effective treatment for this rare severe condition.Case presentationWe report a late preterm Bosnian baby boy (36 weeks) who suffered from a severe form of respiratory distress syndrome with poor response to intensive conventional management and whole exome sequencing revealed homozygous ABCA3 mis-sense mutation. The baby showed remarkable improvement of the respiratory condition after the initiation of Hydroxychloroquine, Azithromycin and Corticosteroids with the continuation of Hydroxychloroquine as a monotherapy till after discharge from the hospital.ConclusionOutcome in patients with ABCA3 mutations is variable ranging from severe irreversible respiratory failure in early infancy to chronic interstitial lung disease in childhood (ChILD) usually with the need for lung transplantation in many patients surviving this rare disorder. Hydroxychloroquine through its anti-inflammatory effects or alteration of intra-cellular metabolism may have an effect in treating cases of ABCA3 gene mutations.

Venoarterial Extracorporeal Membrane Oxygenation for Severe Neonatal Acute Respiratory Distress Syndrome in a Developing Country.

Objective: Extracorporeal membrane oxygenation (ECMO) has supported oxygen delivery and carbon dioxide removal in neonatal severe respiratory failure for more than 4 decades. The definition and diagnosis of neonatal acute respiratory distress syndrome (ARDS) was made according to the criteria first established by a Montreux Conference in 2017. By far, there has been no ECMO efficiency studies in neonatal ARDS. We aimed to compare the outcomes of neonates with severe ARDS supported with and without ECMO.Design: Retrospective pair-matched study.Setting: In the present retrospective pair-matched study, the outcomes of severe ARDS with ECMO support and without ECMO support were analyzed and compared. Propensity score matching was conducted. The study subjects were selected from a China Neonatal ECMO (CNECMO) study. In total, five hospitals were included in the CNECMO study. The patients were matched with demographic and clinical data. The primary endpoint was in-hospital mortality. Secondary outcomes included ventilator-time, ICU stay, hospitalization costs and cranial MRI results.Patients: 145 neonates with severe ARDS (Oxygenation Index, OI ≥16) from 5 hospitals.Interventions: No interventions.Measurements and Main Results: We collected the data of 145 neonates with severe ARDS (Oxygenation Index, OI≥16) from 5 hospitals. Among them, 42 neonates received venoarterial (VA) ECMO support, and the remaining 103 neonates were treated with conventional mechanical ventilation. The mortality of ECMO-supported neonates was not significantly different compared with the ESLO neonatal respiratory-supported from 2012 to 2018 (23.8 vs. 32.5%, p = 0.230). After matching with the propensity score we got 31 pairs. The ECMO-supported neonates had a lower in-hospital mortality (6 of 31, 19.4%) vs. non ECMO-supported patients (18 of 31, 58.1%) (p = 0.002). Hospitalization costs of survivors in ECMO-supported neonates were significantly higher than that of non-ECMO-supported neonates (p < 0.001). There was no difference of ventilator-times (p = 0.206), ICU stay (p = 0.879) and cranial MRI (p = 0.899) between the survivors of ECMO-supported and non–ECMO-supported neonates with ARDS.Conclusions: By far, there has been no ECMO efficiency studies in neonatal ARDS. This study found that ECMO-support have superior outcomes compared with non–ECMO-support in neonates with severe ARDS.

Increased Expression of IL-23 and IL-17 in Serum of Patients with Neonatal Respiratory Distress Syndrome and its Clinical Significance.

The present study focused on the potential clinical significance of Th-17 cell related inflammatory cytokines in the occurrence and development of neonatal respiratory distress syndrome (NRDS). We included 82 NRDS children and 82 healthy controls. NRDS children were divided into the mild and severe group based on the disease severity. The serum samples of the NRDS and non-NRDS children were collected, and the expression levels of IL-17, IL-22, and IL-23 were determined by ELISA method. Moreover, correlation between the levels of the cytokines and the disease severity were analyzed, and receiver operating characteristics curve (ROC) analysis was performed to determine the diagnostic value of the cytokines. Finally, correlation between the lung ultrasound score (LUS) of the NRDS patients and the levels of IL-17 and IL-23 were analyzed. IL-17 and IL-23 were dramatically increased in serum of the NRDS patients compared with the non-NRDS patients; moreover, IL-17 and IL-23 were significantly higher in the severe compared with the mild NRDS group, and the levels of both IL-17 and IL-23 were positively correlated with the disease severity. Furthermore, ROC analysis showed that both IL-17 and IL-23 can distinguish NRDS patient, especially the severe NRDS patients from the non-NRDS patients with high sensitivity and specificity; finally, the levels of IL-17 and IL-23 were positively correlated with the LUS in NRDS patients. IL-17 and IL-23 were up-regulated in NRDS and may serve as sensitive biomarkers for the diagnosis and treatment of the disease.

Full versus half dose of antenatal betamethasone to prevent severe neonatal respiratory distress syndrome associated with preterm birth: study protocol for a randomised, multicenter, double blind, placebo-controlled, non-inferiority trial (BETADOSE)

BackgroundAlthough antenatal betamethasone is recommended worldwide for women at risk of preterm delivery, concerns persist regarding the long-term effects associated with this treatment. Indeed, adverse events, mainly dose-related, have been reported. The current recommended dose of antenatal betamethasone directly derives from sheep experiments performed in the late 60’s and has not been challenged in 45 years. Therefore, randomized trials evaluating novel dose regimens are urgently needed.MethodsA randomised, double blind, placebo-controlled, non-inferiority trial will be performed in 37 French level 3 maternity units. Women with a singleton pregnancy at risk of preterm delivery before 32 weeks of gestation having already received a first 11.4 mg injection of betamethasone will be randomised to receive either a second injection of 11.4 mg betamethasone (full dose arm) or placebo (half dose arm) administered intramuscularly 24 h after the first injection. The primary binary outcome will be the occurrence of severe respiratory distress syndrome (RDS), defined as the need for exogenous intra-tracheal surfactant in the first 48 h of life. Considering that 20% of the pregnant women receiving the full dose regimen would have a neonate with severe RDS, 1571 patients in each treatment group are required to show that the half dose regimen is not inferior to the full dose, that is the difference in severe RDS rate do not exceed 4% (corresponding to a Relative Risk of 20%), with a 1-sided 2.5% type-1 error and a 80% power. Interim analyses will be done after every 300 neonates who reach the primary outcome on the basis of intention-to-treat, using a group-sequential non-inferiority design.DiscussionIf the 50% reduced antenatal betamethasone dose is shown to be non-inferior to the full dose to prevent severe RDS associated with preterm birth, then it should be used consistently in women at risk of preterm delivery and would be of great importance to their children.Trial registrationClinicalTrials.gov identifier: NCT 02897076 (registration date 09/13/2016).

Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid in neonatal respiratory distress syndrome and prognosis.

This study was designed to investigate the correlation between expression levels of cysteine aspartic protease-3 (caspase-3) and B-cell lymphoma gene-2 (Bcl-2) proteins in alveolar lavage fluid and the prognosis of infants with neonatal respiratory distress syndrome (RDS). A total of 150 infants with neonatal RDS undergoing alveolar lavages were divided into four groups: RDS1 (group A, n=42), RDS2 (group B, n=38), RDS3 (group C, n=38) and RDS4 (group D, n=32) according to their thoracic X-ray film grading. The oxygen uptake score, oxygenation saturation, mean airway pressure and expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid of the infants in the four groups were measured and compared. Our results showed higher grading by thoracic X-rays in patients with increased oxygen uptake score, oxygenation index, mean airway pressure, caspase-3 expression level, hospital stay, complications and death rates in all groups; however, the expression levels of Bcl-2 were decreased in those cases, and the differences had statistical significance among the four groups (P<0.05). Analyses for correlation showed a caspase-3 positive area that was positively correlated with oxygen uptake score, oxygenation index and mean airway pressure (P<0.05); and a Bcl-2 expression level that was negatively correlated with oxygen uptake score, oxygenation index and mean airway pressure (P<0.05). Based on our findings, the severity of neonatal RDS is positively correlated with the concentration of caspase-3 in alveolar lavage fluid, and negatively correlated with the expression level of Bcl-2.

Treatment of non-oliguric hyperkalaemia with inhaled salbutamol in premature infants with severe respiratory distress syndrome

Non-oliguric hyperkalaemia (NOHK) in neonates is defined as a plasma potassium level > 6.5 mmol/L in the presence of urine output ≥ 1 mL/kg/h during the first 72 hours of life. It is characterized by a rapid rise of serum potassium to excessively high values, a high risk of cardiac arrhythmias and no occurrence after 72 hours of birth. NOHK commonly occurs in premature neonates, especially in those with a ges-tational age <28 weeks, with only a few reports of this entity in moderate or late preterm neonates. The effectiveness and safety of different treatments for NOHK is uncertain and currently there is no firm treatment recommendation. We describe the case of a moderately premature neo-nate (32+ 2 weeks gestation), with severe neonatal respiratory distress syndrome, who developed NOHK that was treated with inhaled salbutamol. When salbuta-mol is used for the treatment of NOHK, an initial paradoxical rise in potassium levels should always be taken into account to avoid cardiac arrhythmias.

Functional Characterization of ATP-Binding Cassette Transporter A3 Mutations from Infants with Respiratory Distress Syndrome.

Mutations in the ATP-binding cassette transporter A3 gene (ABCA3) result in severe neonatal respiratory distress syndrome and childhood interstitial lung disease. As most ABCA3 mutations are rare or private, determination of mutation pathogenicity is often based on results from in silico prediction tools, identification in unrelated diseased individuals, statistical association studies, or expert opinion. Functional biologic studies of ABCA3 mutations are needed to confirm mutation pathogenicity and inform clinical decision making. Our objective was to functionally characterize two ABCA3 mutations (p.R288K and p.R1474W) identified among term and late-preterm infants with respiratory distress syndrome with unclear pathogenicity in a genetically versatile model system. We performed transient transfection of HEK293T cells with wild-type or mutant ABCA3 alleles to assess protein processing with immunoblotting. We used transduction of A549 cells with adenoviral vectors, which concurrently silenced endogenous ABCA3 and expressed either wild-type or mutant ABCA3 alleles (p.R288K and p.R1474W) to assess immunofluorescent localization, ATPase activity, and organelle ultrastructure. Both ABCA3 mutations (p.R288K and p.R1474W) encoded proteins with reduced ATPase activity but with normal intracellular localization and protein processing. Ultrastructural phenotypes of lamellar body-like vesicles in A549 cells transduced with mutant alleles were similar to wild type. Mutant proteins encoded by ABCA3 mutations p.R288K and p.R1474W had reduced ATPase activity, a biologically plausible explanation for disruption of surfactant metabolism by impaired phospholipid transport into the lamellar body. These results also demonstrate the usefulness of a genetically versatile, human model system for functional characterization of ABCA3 mutations with unclear pathogenicity.

Efficacy of volume target pressure control and synchronized intermittent mandatory ventilation in treating neonatal respiratory distress syndrome

Objective To investigate the efficacy of volume target pressure control(VTPC) and synchronized intermittent mandatory ventilation (SIMV)in treating severe neonatal respiratory distress syndrome (NRDS). Methods Fifty-six admitted cases with severe NRDS hospitalized in Jiangmen Central Hospital from October 2012 to March 2015 were randomly divided into 2 groups: 28 cases in VTPC group were treated by VTPC and SIMV, and 28 cases in pressure control ventilation (PCV)group were treated by PCV and SIMV.There was no significant difference between 2 groups in terms of gender, gestational age, and birth weight (all P>0.05). Artery blood gas analysis was performed at 6 hours, 12 hours, 24 hours, and 48 hours respectively after ventilation.The following parameters were observed: the time of invasive mechanical ventilation, duration of oxygen therapy, mortality and the incidence rates of hypocapnia, pneumothorax, ventilator associated pneumonia (VAP), grade Ⅲ-Ⅳ periventricular intraventricular hemorrhage (PVH-IVH), periventricular leukomalacia (PVL)and bronchopulmonary dysplasia (BPD). Results No case in 2 groups withdrew from the test.There was no significant difference between 2 groups in terms of the first treatment time and total doses of poractant alfa injection (all P>0.05). The time of invasive mechanical ventilation in VTPC group[(71.75±9.82) h] was shorter than that in PVC group[(97.89±16.88) h] (t=7.083, P=0.000). Hypocapnia incidence of four blood gas analysis in VTPC group[(19.64±14.20)%] was lower than that in PCV group[(47.32±18.43)%] (t=6.294, P=0.000). Incidence rates of VAP and PVL in VTPC group were lower than those in PCV group (χ2=5.197, P=0.023; χ2=4.766, P=0.029). However, duration of oxygen therapy, mortality and the incidence rates of pneumothorax, Ⅲ-Ⅳ PVH-IVH and BPD were not significantly different between 2 groups (all P>0.05). Conclusion VTPC+ SIMV has a better efficacy than PCV+ SIMV in the treatment of NRDS. Key words: Mechanical ventilation; Respiratory distress syndrome; Treatment; Infant, premature

Risk factors of death from severe neonatal respiratory distress syndrome

Objective To explore the death risk factors of preterm infants with respiratory distress syndrome (RDS). Methods A retrospective analysis of 66 preterm infants with severe RDS, who admitted to our NICU between January 2010 and December 2011.The patients were divided into the death group and survival group according to the ending. Results There were a total of 24 cases died (36.36%). The death group′s mechanical ventilation time, the median of base excess, the minimum median of pH, PaO2/FiO2, average gestational age, average birth weight, 1 minute Apgar score and 5 minute Apgar score were all lower than those of survival group (P 60%, intrauterine distress, polyembryony, sore for neonatal acute physiology perinatal extension version Ⅱ(SNAPPE-Ⅱ) score were all higher than those of survival group (P 0.05). Further Logistic regression analysis showed that independent risk factors were birth weight, 1 minute Apgar score and SNAPPE-Ⅱ score, OR were 0.990, 0.141 and 1.240 respectively.Receiver operating characteristic analysis of the ability of SNAPPE-Ⅱ score predicting death risk showed the area under curve was 0.86, the difference was statistically significant compared with 0.5 (P=0.000). Death risk prediction showed that the demarcation point SNAPPE-Ⅱ score=24.50 corresponded to the maximum (Youden index=0.70) correct prediction effect. Conclusion Independent risk factors of died from severe RDS are birth weight, 1 minute Apgar score and SNAPPE-Ⅱ scores; SNAPPE-Ⅱ score predicts risk of death from severe RDS accuracy is medium, equal to 24.50 is the best accuracy to the death risk prediction. Key words: Neonatal respiratory distress syndrome; Death; Risk factors; Premature infants

Neonatal Respiratory Distress Syndrome: Early Diagnosis, Prevention, and Treatment

to improve treatment results in premature infants with neonatal respiratory distress syndrome (NRDS), by establishing developmental mechanisms and elaborating methods for its early diagnosis, treatment, and prevention. Material and methods . The paper analyzes the results of a clinical observation and laboratory, instrumental, immunological, morphological, and radiological studies of 320 premature neonates at 26—35 weeks gestational age. The following groups of neonates were identified: 1) 40 premature neonatal infants without NRDS and with the physiological course of an early neonatal period (a comparison group); 2) 190 premature neonates with severe NRDS in whom the efficiency of therapy with exogenous surfactants, such as surfactant BL versus curosurf, was evaluated; 3) 90 premature newborn infants who had died from NRDS at its different stages. Results . The poor maternal somatic, obstetric, and gynecological histories in the early periods of the current pregnancy create prerequisites for its termination, favor the development of severe acute gestosis, and cause abnormal placental changes. Each gestational age is marked by certain placental changes that promote impaired uterineplacentalfetal blood flow and premature birth. Alveolar and bronchial epithelial damages, including those ante and intranatally, microcircula tory disorders play a leading role in the tanatogenesis of NRDS. Intranatal hypoxia and amniotic fluid aspiration are one of the important factors contributing to alveolar epithelial damage and NRDS in premature neonates. Exogenous surfactants prevent the development of hyaline membranes and are useful in the normalization of ventilation-perfusion relationships and lung biomechanical properties. Conclusion. This study could improve the diagnosis and treatment of NRDS, which assisted in reducing the duration of mechanical ventilation from 130±7.6 to 65±11.6 hours, the number of complications (the incidence of intragastric hemorrhages decreased from 28.8 to 9%), the stay length of the neonates in an intensive care unit, and early neonatal mortality rates from 9.3 to 0.9‰ and in improving demographic indicators.

Clinical value of targeted tidal volume in treatment of neonatal respiratory distress syndrome

Objective To explore the effect and complication of synchronized intermittent mandatory ventilation(SIMV) combined with pressure support ventilation(PSV) and targeted tidal volume(TTV) in treatment of neonatal respiratory distress syndrome(NRDS). Methods Fifty-three neonates with severe NRDS between Jan.2010 and Dec.2012 were randomly assigned to 2 groups according to the ventilation mode: SIMV+ PSV+ TTV group(n=27), and assist/control group(A/C group)(n=26). The oxygenation status, the durations of oxygen exposure and ventilation and the incidence of complications were observed. Results The oxygenation status arterial oxygen partial pressure/fraction of inspired oxygen (P/F), arterial oxygen partial pressure /alveolar O2 tension(a/APO2) in the SIMV+ PSV+ TTV group were significantly improved at 6 h after ventilation(t=9.393, 4.856, all P 0.05). Conclusions Compared with A/C, SIMV+ PSV+ TTV can improve the oxygenation status more quickly, and decrease the incidences of air leak syndrome and VAP in neonates with severe RDS. Key words: Synchronized intermittent mandatory ventilation; Targeted tidal volume ventilation; Assist/control ventilation; Respiratory distress syndrome; Neonate