A randomized, controlled trial of poractant alfa versus beractant in the treatment of preterm infants with respiratory distress syndrome

We prospectively evaluated the differences in clinical responses and short-term outcomes in preterm infants with respiratory distress syndrome (RDS) treated with poractant alfa or beractant. Premature infants with RDS were randomized to poractant alfa or beractant treatment between July 2008 and June 2009. Patients were followed until 40 weeks of corrected gestational age or death. The fraction of inspired oxygen (Fio(2)) after surfactant treatment, need for repeat doses, and duration of respiratory support and hospitalization were evaluated between groups. Sixty-one infants received poractant alfa and 65 received beractant. Significantly more patients in the beractant group required ≥2 doses of surfactant compared with the poractant alfa group (31% versus 12%, p = 0.023). Extubation rate within the first 3 days after surfactant administration was higher in the poractant alfa group than in the beractant group (81% versus 55.9%, p = 0.004). Posttreatment Fio(2) requirement in the poractant alfa group was significantly lower than in the beractant group on days 1, 3, and 5. Overall mortality and morbidities were similar between groups. Survival free of bronchopulmonary dysplasia (BPD) at the end of study period was 78.7% and 58.5% in poractant alfa and beractant groups, respectively (p = 0.015). Our study confirms the rapid onset of action, less need for redosing, rapid extubation, and higher survival free of BPD in preterm infants treated with poractant alfa.     

N-SIPPV versus bi-level N-CPAP for early treatment of respiratory distress syndrome in preterm infants

Abstract

Objective: Non-invasive ventilation (NIV) for RDS in extremely/very low birth-weight infants represents the new challenge for neonatologists. In this regard, data comparing the effectiveness of Bi-Level-NCPAP (BiPAP) versus nasal synchronized intermittent positive pressure ventilation (NSIPPV) as primary mode of treatment for RDS are lacking.

Study design: We conducted a retrospective study from December 2007 to December 2010 in seventy-eight infants, who received NIV (N-SIPPV: 33; BiPAP: 45). The primary outcomes were the length and failure of NIV. Secondary outcomes were adverse short-long term pulmonary outcomes, multiple doses of surfactant and others.

Results: There were no significant differences (p?>?0.05) between the two different NIV modes.

Conclusion: The present findings suggest that N-SIPPV and BiPAP gives similar results in the RDS treatment. We did not find a benefit of one over the other ventilation mode and both could be constitute a valid option to conventional mechanical ventilation. The theoretical benefits of these two different methods of NIV are tidal volume enhancement, improvements of the functional residual capacity and of the mean airway pressure and reducing apnea episodes. Further randomized studies to assess the advantages and the efficacy of different methods of NIV for the treatment of the RDS are needed.     

Effects of surfactant treatment in late preterm infants with respiratory distress syndrome

Objective: To evaluate surfactant effectiveness for the treatment of respiratory distress syndrome (RDS) in late preterm infants.

Methods: We performed a retrospective cohort study of infants born between 34⁺⁰ and 36^+6? weeks of gestation admitted for respiratory failure in seven perinatal centers from January 2010 to December 2014. We evaluated changes of FiO₂, PaO₂ and a/APO₂ in surfactant-treated patients, and the need and duration of MV, the duration of noninvasive respiratory support, stay in NICU and in hospital in surfactant-treated and untreated late preterm infants with RDS alone.

Results: We studied 562 infants with RDS, 252 (45%) were treated with surfactant and 310 (55%) were not. FiO₂, PaO₂ and a/APO₂ significantly improved after surfactant treatment. The adjusted odds ratio for the need of MV and the adjusted differences of duration of noninvasive respiratory support, and of NICU and hospital stay were not different in the surfactant and non-surfactant groups.

Conclusions: Surfactant therapy was followed by a quick and persisting significant improvement of respiratory function in late preterm infants with RDS. Surfactant did not improve short-term outcomes in our population probably because other factors such as the gestational age, occurrence of complications and poor feeding play a relevant role.     

Inhaled nitric oxide for the treatment of preterm infants with respiratory distress syndrome

Many authors have hypothesized that inhaled nitric oxide (iNO) might acutely improve oxygenation in preterm neonates with infant respiratory distress syndrome (iRDS) and decrease the risk of bronchopulmonary dysplasia. The studies on the effects of iNO in preterm infants with iRDS have given contradictory results. We report their main methodological characteristics and the observed effects of iNO in preterm infants. Moreover, we discuss the infants' age at the beginning of the study, the dose and duration of iNO therapy, its potential effect on neurodevelopment, its relationship with surfactant properties, and the need to identify patients who are likely to respond to this therapy. We advise caution against the widespread use of iNO in preterm infants with iRDS. At present, it appears to be premature to have specific recommendations regarding the indications for iNO therapy in this group of patients. The conclusion of current trials and the follow-up studies of recently completed trials will give further data to guide neonatologists' decisions, and until then it is likely that clinicians will continue to make case-by-case decisions for the treatment of iNO in preterm infants with hypoxia that is unresponsive to other therapies. However, this decision should always be discussed with the parents.     

Comparison of non-synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as post-extubation respiratory support in preterm infants with respiratory distress syndrome: a randomized controlled trial

Objective: To determine whether post-extubation respiratory support via nsNIPPV decreases the need for mechanical ventilation (MV) compared to nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS).

Methods: In this randomized, controlled, open, prospective, single-center clinical trial, we randomly assigned preterm ventilated infants with RDS to either nsNIPPV or NCPAP after extubation. The primary outcome, extubation failure, was defined by pre-specified failure criteria in the 72 hours after extubation.

Results: A total of 63 preterm ventilated infants were randomized to receive either nsNIPPV (n?=?31) or NCPAP (n?=?32). Extubation failure occurred in six (19.3%) of nsNIPPV group compared with nine (28.12%) of NCPAP group and was statistically not significant (p?=?0.55). The duration of NIV was significantly lower in nsNIPPV group as compared to NCPAP group (40.4?±?39.3 hours versus 111.8?±?116.4 hours, p?=?0.003). The duration of supplementary oxygen was significantly lower in nsNIPPV versus NCPAP group (84.9?±?92.1 hours versus 190.1?±?140.5 hours, p?=?0.002). The rates of BPD in nsNIPPV group (2/29, 6.9%) were significantly lower than in NCPAP group (9/28, 32.14%) (p?=?0.02).

Conclusions: Compared to NCPAP, nsNIPPV appears to be a feasible mode of extubation in preterm infants with significant beneficial effects of reduced duration of NIV support, supplementary oxygen and decreased rates of BPD.     

A randomized trial of inhaled versus intravenous steroids in ventilator-dependent preterm infants.

OBJECTIVE: Intravenous steroids improve the respiratory course in ventilator-dependent preterm infants but have adverse effects. We hypothesized that inhaled steroids would be as effective, but with less systemic effects. STUDY DESIGN: We conducted a randomized, prospective trial comparing inhaled beclomethasone, either 400 or 800 microg/d, to intravenous dexamethasone in preterm infants dependent on conventional mechanical ventilation and supplemental oxygen at 2 weeks of age. RESULTS: Seventy-eight infants were randomized. By day three of therapy, the intravenous steroid group had significantly decreased ventilator and oxygen requirements compared to either inhaled group. The inhaled 800-microg/d group trended toward more rapid decreases in ventilator and oxygen requirements than the 400-microg/d group. By day 14, all groups had similar reductions in ventilator and oxygen requirements. The incidence of adverse effects did not differ between groups. CONCLUSIONS: In this small, randomized study, inhaled steroids conferred no advantages to intravenous steroids in the management of ventilator-dependent preterm infants.     

Severe bronchopulmonary dysplasia – incidence and predictive factors in a prospective,multicenter study in very preterm infants with respiratory distress syndrome

Background: Severe bronchopulmonary dysplasia (BPD) remains a major complication of prematurity and can have significant impact on long-term pulmonary sequelae and adverse neurodevelopmental outcomes.

Objective: To assess the incidence and evaluate the predictive factors for severe BPD in very preterm infants with respiratory distress syndrome.

Methods: Of the 846 premature infants born at ≤32-week gestation who developed respiratory distress syndrome (RDS), 707 infants with known oxygen dependency at 36 weeks gestational age were included in the analysis of BPD incidence. With univariate and multiple logistic regression models we evaluated the risk factors for the development of severe BPD and calculated odds ratios (ORs).

Results: The overall incidence of BPD was 45.2%. Severe BPD accounted for 6%, with morbidity pertaining mainly to infants <29-week gestation (incidence 10%). The risk factors for severe BPD included male gender (OR 3.02 95%CI 1.30–7.46), intubation in the delivery room (OR 2.57, 95%CI 1.00–7.18), and invasive ventilation >7 days (OR 7.05, 95%CI 2.63–22.4). The protective factors were early continuous positive airway pressure (CPAP) in the univariate analysis and receiving surfactant <15?min after birth in the multivariate model.

Conclusions: Mechanical ventilation >7 days is the most prevalent risk factor for severe BPD. CPAP initiated in the delivery room and early surfactant are key preventive measures.     

Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial

In a prospective, randomized, double-blind, multicentre trial the effect of antenatal treatment with betamethasone phosphate was compared with placebo in the prevention of the respiratory distress syndrome (RDS) in preterm infants. The dose of betamethasone was 4 mg every 8 h for six doses, unless delivery occurred. The 251 women who were enrolled gave birth to 262 liveborn infants, 130 in the beta-methasone and 132 in the placebo group; the two groups were evenly matched in most respects. The diagnosis of RDS in the newborn was confirmed by two independent assessors. Seven of the 130 infants in the betamethasone group and 16 of the 132 in the placebo group developed RDS. In infants whose mothers had received at least three injections, RDS was also less frequent in the steroid group than in the placebo group (3/104 and 10/104 respectively; P less than 0.05). There was a significant reduction of RDS in those born between 24 h and 6 days after entry into the trial (0/30 and 8/45 respectively; P less than 0.05). The largest difference in frequency of RDS occurred in the subgroup of infants born before 34 weeks gestation, within 8 days of trial entry, and whose mothers had received at least three injections (0/27 steroid group and 7/32 placebo group; P = 0.03), and there were also significantly fewer neonatal deaths (2/27 and 13/32, respectively; P less than 0.01) in this subgroup. Betamethasone did not provoke earlier delivery. Premature rupture of the membranes and maternal hypertension did not seem to contraindicate the use of steroids: there was no increase in maternal or neonatal sepsis nor in stillbirth in hypertensive pregnancies in the steroid group. Neonatal jaundice was significantly less frequent in the steroid (55/129) than in the placebo group (81/127; P less than 0.01) but not in the subgroups born before 34 completed weeks gestation.     

Early neonatal outcomes of volume guaranteed ventilation in preterm infants with respiratory distress syndrome

Background: Volume guaranteed (VG) synchronized intermittent mandatory ventilation (SIMV) is a novel mode of SIMV that provides automatic adjustment of the peak inspiratory pressure for ensuring a minimum set tidal volume and there are limited data about the effects of VG ventilation on short term neonatal outcomes in preterm infants with respiratory distress syndrome (RDS). Objective: The main objective of this study was to evaluate the effect of VG ventilation on duration of ventilation and total supplemental oxygen. We also aimed to compare the early neonatal outcomes of VG ventilation versus conventional SIMV on short-term outcomes in preterm babies with RDS who were given surfactant. Methods: In this randomized controlled study, preterm infants who were admitted with RDS and given surfactant were divided into 2 groups: group 1 included infants ventilated on conventional SIMV (n = 30) and group 2 included infants ventilated on VG ventilation (n = 42). Neonatal morbidities such as air leak, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and duration of mechanical ventilation and total oxygen supplementation were all recorded. Results: There were no significant differences between two groups in terms of demographic features. Infants ventilated with VG mode had significantly shorter duration of ventilation and need of total supplemental oxygen. The incidences of oxygen related short term complications including BPD, ROP, and IVH were also significantly lower in these infants compared with those ventilated with conventional SIMV. No significant differences were found between two groups with respect to NEC and air leak. Conclusion: In conclusion, VG ventilation in combination with surfactant treatment significantly reduced both duration of mechanical ventilation and early neonatal oxygen related morbidities including BPD, ROP and IVH in preterm infants with RDS. This data favors the use of VG ventilation in respiratory support of premature infants.     

Cord serum lipid and apolipoprotein levels in preterm infants with the neonatal respiratory distress syndrome

Objective: The purpose of this study was to evaluate the effects of birth weight on cord serum lipid and apolipoprotein levels in preterm infants with and without respiratory distress syndrome (RDS). Methods: Cord serum lipid and apolipoprotein levels were evaluated in preterm infants (39 with RDS and 68 controls without RDS). Based on morbidity and mortality risk, RDS and non-RDS infants were separated into four birth weight groups (2000-2499 g, 1500-1999 g, 1000-1499 g, < 1000 g) and evaluated for effects of birth weight on cord serum levels. Results: RDS infants with birth weight of 2000-2499 g had significantly higher levels of cholesterol, triglyceride, total fatty acids and apolipoprotein A-I, but not arachidonic acid, than controls. RDS infants weighing 1000-1999 g had lower total fatty acids and apolipoprotein B levels, including arachidonic acid, than non-RDS infants. Cord serum lipid and apolipoprotein levels were significantly elevated in large (2000-2499 g) RDS infants, but lower levels were found in smaller (1000-1999 g) RDS infants. Conclusions: Cord serum arachidonic acid and apolipoprotein levels found in RDS infants suggest that lipid transport across the placenta may be abnormal. Inadequate total fatty acid supplies in utero could interfere with normal fetal growth and maturation, leading to development of neonatal RDS as one manifestation of risk for postnatal morbidity and mortality.     

Exogenous surfactant for treatment of respiratory distress syndrome in premature infants

A prospective, randomized and controlled trial was conducted to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome (RDS) in infants. Eighteen premature infants with RDS were studied. Group I consisted of 9 premature infants with a mean birth weight of 1,455 +/- 265.9 g and a mean gestational age of 31.4 +/- 1.3 weeks. Group II consisted of 9 premature infants with a mean birth weight of 1,411 +/- 379.0 g and a mean gestational age of 30.6 +/- 1.7 weeks. Reconstituted bovine surfactant (Surfactant TA, Tokyo Tanabe Co., Japan), 120 mg/kg body weight was suspended in 4 ml normal saline and delivered to the lungs of the patients in group I through an endotracheal tube via a catheter in five divided doses (mean age at this point was 5.7 +/- 4.5 hours). An air placebo (4 ml per kilogram) was given to the patients in group II. The results showed that significant improvement in oxygenation, characterized by (1) an increase in the ratio of arterial to alveolar oxygen tension; (2) a decrease in the fractional inspiratory oxygen concentration; and (3) changes in mean airway pressure and ventilatory index, were noted in the surfactant-treated group. Pneumothorax was found in one surfactant-treated infant and one control infant. Pulmonary interstitial emphysema was found in one control infant. One control infant later developed bronchopulmonary dysplasia. Four (44.4%) of the surfactant-treated infants and four (44.4%) of the control infants had evidence of patient ductus arteriosus. The mean duration from birth to extubation in the surfactant-treated infants was 121.9 +/- 1.9 hours.     

早产儿呼吸窘迫综合征的早期预防和治疗

早产儿呼吸窘迫综合征(neonatal respiratory distress syndrome, RDS)通常发生于胎龄较小的极低或超低出生体重儿,主要原因是肺表面活性物质合成少和肺发育不成熟。目前外源性肺表面活性物质的替代治疗是防治早产儿RDS的主要手段,此外,产前预防、产房复苏策略以及出生后早期呼吸支持治疗等综合措施也对该病的预防和治疗起着极为重要的作用。本文主要对早产儿RDS的预防及治疗措施进行讨论。     

Antepartum aminophylline treatment for prevention of the respiratory distress syndrome in premature infants

The frequency of idiopathic respiratory distress (IRD) among premature offspring born of women who were given aminophylline before the thirty-fourth week of pregnancy was evaluated. Sixty-seven premature deliveries were included in the aminophylline group and 75 in the control group. The perinatal death rate was 7.1% in the aminophylline group and 17.9% in the control group (p less than 0.05). A statistically significant difference was noted between the aminophylline and control groups in the frequency of IRD which was three times lower (10%) in the aminophylline group than in the control group (29.5%) for the total of premature infants. If the time of rupture of membranes is taken into consideration, a significant decrease in the frequency of IRD following aminophylline administration is noted in the infants, whose mothers had ruptured membranes for more than 24 hours. No complications or side effects of aminophylline administration were noted in the mothers or their infants.     

Variations in neutrophil count in preterm infants with respiratory distress syndrome who subsequently developed chronic lung disease

Neutrophil counts were studied in 62 preterm infants receiving mechanical ventilation for neonatal respiratory distress syndrome (NRDS). Exploratory analysis indicated that the severity of NRDS, as demonstrated by fractional inspired oxygen (FiO2), mean airway pressure (MAP), arterial-alveolar PO2 ratio (a/APO2) and oxygenation index (OI), was correlated with percentage change of neutrophil counts during the first 5 days of life. Further analysis demonstrated that infants with NRDS who subsequently developed chronic lung disease (CLD) (n = 21) had statistically significant differences in variation of neutrophil counts when compared with the remainder (n = 41) without CLD (-35.0% +/- 4.3 vs. -16.9% +/- 5.8, p < 0.02). It is concluded that significant variations in neutrophil counts during the first 5 days of life may be found in infants with NRDS who subsequently develop CLD and that these changes may have predictive value regarding the development of CLD.