Comparison of High CPAP versus NIPPV in Preterm Neonates: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to compare outcomes following receipt of high continuous positive airway pressure (CPAP) versus nasal intermittent positive pressure ventilation (NIPPV) in extremely preterm neonates. STUDY DESIGN: We retrospectively compared outcomes of preterm neonates (22-28 weeks' gestation) following their first episode of either high CPAP (≥ 9 cm H2O) or NIPPV. Primary outcome was failure of high CPAP or NIPPV within 7 days, as determined by either need for intubation or use of an alternate noninvasive mode. RESULTS: During the 3-year study period, 53 infants received high CPAP, while 119 patients received NIPPV. There were no differences in the primary outcome (adjusted odds ratio 1.21; 95% confidence interval 0.49-3.01). The use of alternate mode of noninvasive support was higher with the use of high CPAP but no other outcome differences were noted. CONCLUSION: Based on this cohort, there was no difference in incidence of failure between high CPAP and NIPPV, although infants receiving high CPAP were more likely to require an alternate mode of noninvasive support. KEY POINTS: · Use of high CPAP pressures (defined as ≥9 cm H2O) is gradually increasing during care of preterm neonates.. · Limited data exists regarding its efficacy and safety.. · This study compares high CPAP with NIPPV, and demonstrates comparable short-term clinical outcomes..

Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates: A Systematic Review and Meta-analysis.

Importance: Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials. Objective: To evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates. Data Sources: MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions. Study Selection: Randomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included. Data Extraction and Synthesis: Two co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis. Main Outcomes and Measures: The 3 prespecified outcomes were sIVH, cPVL, and severe brain injury. Results: A total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], -1% [95% CI, -2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, -5% [95% CI, -8% to -3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, -9% [95% CI, -13% to -5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, -3% [95% CI, -4% to -1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, -4% [95% CI, -7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, -30 [95% CI, -368 to -16]). Conclusions and Relevance: Results of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.

Exploration of Sex and Age-Based Associations in Clinical Characteristics, Predictors of Severity, and Duration of Stay among COVID-19 Patients at the University Hospital of Saudi Arabia.

COVID-19 infection has a spectrum of variable clinical severity between populations because of their characteristic demographic features, co-morbidities, and immune system reactions. This pandemic tested the healthcare system's preparedness, which depends on predictors of severity and factors related to the duration of hospital stays. Therefore, we carried out a single-center, retrospective cohort study in a tertiary academic hospital to investigate these clinical features and predictors of severe disease and study the different factors that affect hospital stay. We utilized medical records from March 2020 to July 2021, which included 443 confirmed (positive RT-PCR) cases. The data were explained using descriptive statistics and analyzed via multivariate models. Among the patients, 65.4% were female and 34.5% were male, with a mean age of 45.7 years (SD ± 17.2). We presented seven age groups with ranges of 10 years and noticed that patients aged 30-39 years old comprised 23.02% of the records, while patients aged 70 and above comprised 10%. Nearly 47% were diagnosed as having mild, 25% as moderate, 18% as asymptomatic, and 11% as having a severe case of COVID-19 disease. Diabetes was the most common co-morbidity factor in 27.6% of patients, followed by hypertension (26.4%). Our population's predictors of severity included pneumonia, identified on a chest X-ray, and co-morbid conditions such as cardiovascular disease, stroke, ICU stay, and mechanical ventilation. The median length of hospital stay was six days. It was significantly longer in patients with a severe disease and who were administered systemic intravenous steroids. An empirical assessment of various clinical parameters could assist in effectively measuring the disease progression and follow-up with patients.

Melatonin for non-operating room sedation in paediatric population: a systematic review and meta-analysis.

CONTEXT: The literature on melatonin as a sedative agent in children is limited. OBJECTIVE: To conduct a systematic review of studies assessing the efficacy and safety of melatonin for non-operating room sedation in children. METHODS: Medline, Embase, Cochrane Library and Cumulative Index to Nursing and Allied Health were searched until 9 April 2020 for studies using melatonin and reporting one of the prespecified outcomes of this review. Two authors independently assessed the eligibility, risk of bias and extracted the data. Studies with a similar study design, comparator and procedure were pooled using the fixed-effect model. RESULTS: 25 studies (clinical trials=3, observational studies=9, descriptive studies=13) were included. Melatonin was used for electroencephalogram (EEG) (n=12), brainstem evoked response audiometry (n=8) and magnetic resonance imaging (MRI) (n=5). No significant differences were noted on meta-analysis of EEG studies comparing melatonin with sleep deprivation (SD) (relative risk (RR) 1.06 (95% CI 0.99 to 1.12)), melatonin with chloral hydrate (RR 0.97 (95% CI 0.89 to 1.05)) and melatonin alone with melatonin and SD combined (RR 1.03 (95% CI 0.97 to 1.10)) for successful procedure completion. However, significantly higher sedation failure was noted in melatonin alone compared with melatonin and SD combined (RR 1.55 (95% CI 1.02 to 2.33)) for EEG. Additionally, meta-analysis showed lower sleep latency for melatonin compared with SD (mean difference -10.21 (95% CI -11.53 to -8.89) for EEG. No major adverse events were reported with melatonin. CONCLUSION: Although several studies were identified, and no serious safety concerns were noted, the evidence was not of high quality to establish melatonin's efficacy for non-operating room sedation in children.

Randomised trial estimating length of endotracheal tube insertion using gestational age or nasal-tragus length in newborns: a study protocol.

INTRODUCTION: Endotracheal tube (ETT) insertion depth estimation is important for optimal placement of ETT tip and balanced ventilation of the lungs. Various methods are available to determine the ETT insertion depth. The Neonatal Resuscitation Programme recommends the gestational age and nasal-tragus length (NTL) methods for estimating ETT insertion depth during cardiopulmonary resuscitation. However, the prospective data comparing these two methods is lacking. METHODS AND ANALYSIS: This is an open-label multi-centre randomised controlled trial, where gestational age and NTL methods will be used to determine the initial ETT insertion depth in term and preterm infants that are less than 28 days old, requiring oral intubation in the delivery room or neonatal intensive care unit (NICU). SITES AND SAMPLE SIZE: The trial is aimed to recruit 454 infants over 3 years across tertiary level NICUs. OUTCOMES: The primary outcome includes an optimally positioned ETT, defined as an ETT tip between the upper border of the first thoracic vertebra and the lower border of the second thoracic vertebra. The outcome is assessed by a paediatric radiologist, who will be masked to the group assignment. Secondary outcomes are malpositioned ETT tips, pneumothorax, ETT repositioning, chronic lung disease, invasive ventilation days, and death. ANALYSIS: Data will be analysed using the intention-to-treat principle. The primary and categorical secondary outcomes will be compared using the χ2 test. Adjusted risk ratios of outcomes will be calculated along with 95% CIs through multivariable logistic regression analysis, including covariates deemed biologically to influence the outcomes. ETHICS AND DISSEMINATION: The study has been approved by the PNU Research Ethics Board (20-0148) and the respective ethical review boards of the participating centres. The results will be disseminated through conference meetings, social media platforms, and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT04393337.

Neurodevelopmental outcomes following bevacizumab treatment for retinopathy of prematurity: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the studies exploring the association between bevacizumab and neurodevelopmental outcomes. METHODS: Embase, Medline, CINAHL, and Cochrane Library databases were searched for studies examining neurodevelopmental outcomes of preterm infants treated with bevacizumab compared to laser ablation or cryotherapy for severe retinopathy of prematurity (ROP). RESULTS: Thirteen studies (clinical trial = 1; cohort studies = 12) were included. Random-effects model meta-analysis showed significant increased odds of cognitive impairment associated with bevacizumab treatment on both unadjusted (unadjusted odds ratio (OR) 1.61; 95% confidence interval (CI) 1.12, 2.30) and adjusted analyses (adjusted OR 1.90; 95% CI 1.22, 2.97). Infants treated with bevacizumab for severe ROP had significantly lower Bayley-III cognitive (mean difference (MD) -1.66; 95% CI -3.21, -0.12), and language composite scores (MD -5.50; 95% CI -8.24, -2.76) compared to infants treated with laser ablation or cryotherapy. CONCLUSION: Bevacizumab treatment for severe ROP is associated with increased risk of cognitive impairment and lower cognitive and language scores in preterm infants.

High CPAP vs. NIPPV in preterm neonates - A physiological cross-over study.

OBJECTIVE: To evaluate the physiological impact of high CPAP (≥9 cmH2O) vs. NIPPV at equivalent mean airway pressures. STUDY DESIGN: In this cross-over study, preterm neonates on high CPAP or NIPPV were placed on the alternate mode. After 30 min, left and right ventricular cardiac output and work of breathing indices were assessed, following which patients were placed back on the original mode and a similar procedure ensued. RESULTS: Fifteen infants with mean (SD) postmenstrual age 32.7 (3.0) weeks, and weight 1569 (564) grams were included. No differences in LVO [320 (63) vs. 331 (86) mL/kg/min, P = 0.46] or RVO [420 (135) vs. 437 (141) mL/kg/min, P = 0.19] were noted during high CPAP vs. NIPPV, along with no differences in work of breathing indices. CONCLUSION: High CPAP pressures did not adversely impact cardiac output or work of breathing compared to NIPPV at equivalent mean airway pressure.

Nasal mask vs binasal prongs for nasal continuous positive airway pressure in preterm infants: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of nasal continuous positive airway pressure (NCPAP) given with nasal masks (NM) compared with binasal prongs (BNP) on the incidence of intubation within 72 hours in preterm infants (primary outcome) via meta-analysis of clinical studies. DATA SOURCES: We searched for randomized clinical trials (RCTs) or quasi-RCTs in Medline, PubMed, and Web of Science from inception through 4 December 2019. DATA EXTRACTION/SYNTHESIS: Two independent co-authors extracting data performed the meta-analysis using a fixed-effect model to yield pooled relative risk (RR) and its 95% confidence interval (CI) for each outcome. We used Cochrane GRADE to evaluate the evidence quality. RESULTS: Eleven RCTs met the inclusion criteria. The meta-analysis showed NCPAP provided via NM significantly reduced the rate of intubation within 72 hours (RR, 0.72; 95% CI, 0.58-0.90; nine studies; GRADE-moderate) and nasal trauma (RR, 0.64; 95% CI, 0.55-0.74; GRADE-low) compared with NCPAP provided via BNP. Also, NCPAP via NM significantly reduced surfactant treatment (RR, 0.85; 95% CI, 0.74-0.97; GRADE-very low) and bronchopulmonary dysplasia (RR, 0.47; 95% CI, 0.23-0.95; GRADE-low) compared with BNP in a setting where NCPAP was used as the primary support in respiratory distress syndrome. No statistically significant differences were noted between groups in secondary outcomes except increased NCPAP duration when NCPAP given with NM compared with BNP (mean difference [days], 1.78; 95% CI, 1.67-1.89; GRADE-low). CONCLUSION: Among premature infants, NCPAP provided with NM is more effective in preventing intubation and mechanical ventilation within 72 hours of initiating the support compared with NCPAP provided with BNP.

Neonatal respiratory outcomes in pregnancy induced hypertension: introducing a novel index.

Objective: To evaluate short-term respiratory outcomes, mortality and bronchopulmonary dysplasia (BPD) in preterm infants born to mothers with and without pregnancy induced hypertension (PIH).Methods: Exposed infants <33 weeks' gestation were matched to controls in a 1:2 ratio, based on gestation, sex and antenatal steroid exposure in this retrospective cohort study. Primary outcomes were a novel cumulative respiratory index (cRI) (product of mean airway pressure-hours and FiO2-hours while on invasive ventilation during first 72 hours), mortality and BPD.Results: Seventy-nine exposed infants were matched with 158 controls. cRI was higher in exposed infants (median 1854; IQR 186-13,901) versus controls (median 1359; IQR 210-11,302) but not statistically significant (p = .63). On conditional regression analysis, PIH did not predict cRI (adjusted ß = 0.96; 95% CI = 0.79-1.17; p = .712). No association between PIH and mortality (unadjusted odds ratio [OR] = 3.14; 95% CI = 0.76-13.0; p=.11) was identified. PIH was significantly associated with BPD on univariate analysis (OR = 2.29; 95% CI = 1.02-5.17; p=.046), but not after adjustment (aOR = 1.26; 95% CI = 0.38-4.19; p=.7).Conclusions: PIH was not associated with cRI, mortality or BPD in this study. Further validation of cRI and exploration of its relationship with PIH as well as neonatal outcomes is warranted.