OBJECTIVES: To determine if prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP regardless of respiratory status (started within the first hour of life), reduces the use of mechanical ventilation and the incidence of bronchopulmonary dysplasia without any adverse effects in preterm infants.
SEARCH METHODS: A comprehensive search was run on 6 November 2020 in the Cochrane Central Register of Controlled Trials (CENTRAL via CRS Web) and MEDLINE via Ovid. We also searched the reference lists of retrieved studies.
SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs in preterm infants (under 37 weeks of gestation). We included trials if they compared prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP (started within the first hour of life) in infants with minimal signs of respiratory distress with 'supportive care', such as supplemental oxygen therapy, standard nasal cannula, or mechanical ventilation. We excluded studies where prophylactic CPAP was compared with CPAP along with co-interventions.
DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal, including independent study selection, assessment of trial quality, and extraction of data by two review authors.
MAIN RESULTS: We included eight trials (seven from the previous version of the review and one new study), recruiting 3201 babies, in the meta-analysis. Four trials, involving 765 babies, compared CPAP with supportive care, and three trials (2364 babies) compared CPAP with mechanical ventilation. One trial (72 babies) compared prophylactic CPAP with very early CPAP. Apart from a lack of blinding of the intervention, we judged seven studies to have a low risk of bias. However, one study had a high risk of selection bias. Prophylactic or very early CPAP compared to supportive care There may be a reduction in failed treatment (risk ratio (RR) 0.6, 95% confidence interval (CI) 0.49 to 0.74; risk difference (RD) -0.16, 95% CI -0.34 to 0.02; 4 studies, 765 infants; very low certainty evidence). CPAP possibly reduces BPD at 36 weeks (RR 0.76, 95% CI 0.51 to 1.14; 3 studies, 683 infants, moderate certainty evidence); there may be little or no difference in death (RR 1.04, 95% CI 0.56 to 1.93; 4 studies, 765 infants; moderate certainty evidence). Prophylactic CPAP may reduce the composite outcome of death or BPD (RR 0.69, 95% CI 0.40 to 1.19; 1 study, 256 infants; low certainty evidence). There may be no difference in pulmonary air leak (pneumothorax) (RR 0.75, 95% CI 0.35 to 1.16; 3 studies, 568 infants; low certainty evidence), or intraventricular haemorrhage (IVH) Grade 3 or 4 (RR 0.96, 95% CI 0.39 to 2.37; 2 studies, 486 infants; moderate certainty evidence). Neurodevelopmental impairment was not reported in any of the studies. Prophylactic or very early CPAP compared to mechanical ventilation There was probably a reduction in the incidence of BPD at 36 weeks (RR 0.89, 95% CI 0.8 to 0.99; RD -0.04, 95% CI -0.08 to 0.00; 3 studies, 2150 infants; moderate certainty evidence); and death or BPD (RR 0.89, 95% CI 0.81 to 0.97; RD -0.05, 95% CI -0.09 to 0.01; 3 studies, 2358 infants; moderate certainty evidence). There was also probably a reduction in the need for mechanical ventilation (failed treatment) (RR 0.49, 95% CI 0.45 to 0.54; RD -0.50, 95% CI -0.54 to -0.45; 2 studies, 1042 infants; moderate certainty evidence). There was probably a reduction in the incidence of death (RR 0.82, 95% CI 0.66 to 1.03; 3 studies, 2358 infants; moderate certainty evidence); pulmonary air leak (pneumothorax) (RR 1.24, 95% CI 0.91 to 1.69; 3 studies, 2357 infants; low certainty evidence); and IVH Grade 3 or 4 (RR 1.09, 95% CI 0.86 to 1.39; 3 studies, 2301 infants; moderate certainty evidence). One study in this comparison reported that there was probably little or no difference between the groups in the incidence of neurodevelopmental impairment at 18 to 22 months (RR 0.91, 95% CI 0.62 to 1.32; 976 infants; moderate certainty evidence). Prophylactic CPAP compared with very early CPAP There was one study in this comparison. We are very uncertain whether there is any difference in the incidence of BPD (RR 0.5, 95% CI 0.05 to 5.27; very low certainty evidence). The combined outcome of death and BPD was not reported, and failed treatment was reported but without data. There may have been little to no effect on death (RR 0.75, 95% CI 0.29 to1.94; 1 study, 72 infants; very low certainty evidence). Intraventricular haemorrhage Grade 3 or 4 and neurodevelopmental outcomes were not reported in this study. Pulmonary air leak (pneumothorax) was reported in this study, but there were no events in either group.
AUTHORS' CONCLUSIONS: For preterm and very preterm infants, there is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. When compared to mechanical ventilation, prophylactic nasal CPAP in very preterm infants reduces the incidence of BPD, the combined outcome of death and BPD, and mechanical ventilation. There is probably no difference in neurodevelopmental impairment at 18 to 22 months of age. When prophylactic CPAP is compared to early CPAP, we are very uncertain about whether there is any difference between prophylactic and very early CPAP. There is no information about the effect of prophylactic or very early CPAP in late preterm infants. There is one study awaiting classification.
MATERIALS AND METHODS: A single-centre, prospective, casecontrol study involving 32 subjects of preterm neonates was conducted at a tertiary care hospital in Malang, East Java, Indonesia between January to June 2022. A total of 15 preterm neonates with NEC and 17 preterm neonates without NEC were enrolled in this study. Data on demographic, clinical and laboratory findings were collected. Multiple logistic regression test was performed to analyse the risk factors for NEC development. Further profiling within 15 subjects with NEC, i.e., NEC grade ≥ II, were conducted to collect systemic, abdominal, laboratory, abdominal x-ray (AXR) and blood culture findings.
RESULTS: The risk factors related to NEC development in preterm infants were multi-morbidity (adjusted OR = 11.96; 95% CI 1.85 168.38; p = 0.046), antibiotic exposure (OR = 15.95; 95% CI 1.54 165.08; p = 0.020) and requiring advanced neonatal resuscitation at birth (OR = 10.04; 95% CI 1.09 92.11; p = 0.041). Further profiling within NEC cohorts highlighted respiratory distress (86.7%), (oro)gastric retention (80.0%), thrombocytopenia (53.3%), gastrointestinal dilatation in AXR (53.3%), and positive blood culture Klebsiella pneumoniae (40.0%) were most common findings.
CONCLUSION: Preterm neonates with multimorbidity, prolonged antibiotic exposure, and requiring advanced resuscitation at birth were more likely to develop NEC. Early detection of the risk factors and determinant factors for survival may help to improve the clinical outcome.
OBJECTIVES: To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.
SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.
SELECTION CRITERIA: We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.
MAIN RESULTS: We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO2 Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS: Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO2 ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.
DESIGN: A quasi-experimental and longitudinal study was conducted among mothers with premature infants.
METHODS: Forty-eight mother-infant dyads were enrolled per arm in the control and experimental groups. The control group received standard routine care, while the experimental group received a maternal kangaroo care education program. Data were collected through self-administered Kangaroo Care Questionnaires. Chi-square, the general linear model and repeated measures ANOVA were used to analyse data.
RESULTS: The demographics are a majority of Malay mothers with multipara, a caesarean delivery with prematurity. At 3 months post-intervention, the experimental group reported a significant reduction in stress, a positive perception and good knowledge towards kangaroo care implementation. The mothers' perceived barriers towards kangaroo care significantly decreased after 3 months in the experimental group.
CONCLUSION: Exposing preterm infants to either 12 h cyglical lighting or continuously dim environment did not have any significant effect on their weight gain during the neonatal period.
OBJECTIVES: • To determine if early compared with delayed initiation of CPAP results in lower mortality and reduced need for intermittent positive-pressure ventilation in preterm infants in respiratory distress ○ Subgroup analyses were planned a priori on the basis of weight (with subdivisions at 1000 grams and 1500 grams), gestation (with subdivisions at 28 and 32 weeks), and according to whether surfactant was used ▫ Sensitivity analyses based on trial quality were also planned ○ For this update, we have excluded trials using continuous negative pressure SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 6), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL), on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA: We included trials that used random or quasi-random allocation to either early or delayed CPAP for spontaneously breathing preterm infants in respiratory distress.
DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of trial quality and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS: We found four studies that recruited a total of 119 infants. Two were quasi-randomised, and the other two did not provide details on the method of randomisation or allocation used. None of these studies used blinding of the intervention or the outcome assessor. Evidence showed uncertainty about whether early CPAP has an effect on subsequent use of intermittent positive-pressure ventilation (IPPV) (typical risk ratio (RR) 0.77, 95% confidence interval (CI) 0.43 to 1.38; typical risk difference (RD) -0.08, 95% CI -0.23 to 0.08; I² = 0%, 4 studies, 119 infants; very low-certainty evidence) or mortality (typical RR 0.93, 95% CI 0.43 to 2.03; typical RD -0.02, 95% CI -0.15 to 0.12; I² = 33%, 4 studies, 119 infants; very low-certainty evidence). The outcome 'failed treatment' was not reported in any of these studies. There was an uncertain effect on air leak (pneumothorax) (typical RR 1.09, 95% CI 0.39 to 3.04, I² = 0%, 3 studies, 98 infants; very low-certainty evidence). No trials reported intraventricular haemorrhage or necrotising enterocolitis. No cases of retinopathy of prematurity were reported in one study (21 infants). One case of bronchopulmonary dysplasia was reported in each group in one study involving 29 infants. Long-term outcomes were not reported.
AUTHORS' CONCLUSIONS: All four small trials included in this review were performed in the 1970s or the early 1980s, and we are very uncertain whether early application of CPAP confers clinical benefit in the treatment of respiratory distress, or whether it is associated with any adverse effects. Further trials should be directed towards establishing the appropriate level of CPAP and the timing and method of administration of surfactant when used along with CPAP.
METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.
RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).
CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.