Typical Risk Ratio Research Articles

Non-pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.

Pain, when treated inadequately, puts preterm infants at a greater risk of developing clinical and behavioural sequelae because of their immature pain system. Preterm infants in need of intensive care are repeatedly and persistently exposed to noxious stimuli, and this happens during a critical window of their brain development with peak rates of brain growth, exuberant synaptogenesis and the developmental regulation of specific receptor populations. Nearly two-thirds of infants born at less than 29 weeks' gestation require mechanical ventilation for some duration during the newborn period. These neonates are endotracheally intubated and require repeated endotracheal suctioning. Endotracheal suctioning is identified as one of the most frequent and most painful procedures in premature infants, causing moderate to severe pain. Even with improved nursing performance and standard procedures based on neonatal needs, endotracheal suctioning remains associated with mild pain. To evaluate the benefits and harms of non-pharmacological interventions for the prevention of pain during endotracheal suctioning in mechanically ventilated neonates. Non-pharmacological interventions were compared to no intervention, standard care or another non-pharmacological intervention. We conducted searches in June 2023 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Embase, CINAHL and three trial registries. We searched the reference lists of related systematic reviews, and of studies selected for inclusion. We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs that included term and preterm neonates who were mechanically ventilated via endotracheal tube or via tracheostomy tube and required endotracheal suctioning performed by doctors, nurses, physiotherapists or other healthcare professionals. Our main outcome measures were validated composite pain scores (including a combination of behavioural, physiological and contextual indicators). Secondary outcomes included separate physiological and behavioural pain indicators. We used standard methodological procedures expected by Cochrane. For continuous outcome measures, we used a fixed-effect model and reported mean differences (MDs) with 95% confidence intervals (CIs). For categorical outcomes, we reported the typical risk ratio (RR) and risk difference (RD) and 95% CIs. We assessed risk of bias using the Cochrane RoB 1 tool, and assessed the certainty of the evidence using GRADE. We included eight RCTs (nine reports), which enroled 386 infants, in our review. Five of the eight studies were included in a meta-analysis. All studies enrolled preterm neonates. Facilitated tucking versus standard care (four studies) Facilitated tucking probably reduces Premature Infant Pain Profile (PIPP) score during endotracheal suctioning (MD -2.76, 95% CI 3.57 to 1.96; I² = 82%; 4 studies, 148 infants; moderate-certainty evidence). Facilitated tucking probably has little or no effect during endotracheal suctioning on: heart rate (MD -3.06 beats per minute (bpm), 95% CI -9.33 to 3.21; I² = 0%; 2 studies, 80 infants; low-certainty evidence); oxygen saturation (MD 0.87, 95% CI -1.33 to 3.08; I² = 0%; 2 studies, 80 infants; low-certainty evidence); or stress and defensive behaviours (SDB) (MD -1.20, 95% CI -3.47 to 1.07; 1 study, 20 infants; low-certainty evidence). Facilitated tucking may result in a slight increase in self-regulatory behaviours (SRB) during endotracheal suctioning (MD 0.90, 95% CI 0.20 to 1.60; 1 study, 20 infants; low-certainty evidence). No studies reported intraventricular haemorrhage (IVH). Familiar odour versus standard care (one study) Familiar odour during endotracheal suctioning probably has little or no effect on: PIPP score (MD -0.30, 95% CI -2.15 to 1.55; 1 study, 40 infants; low-certainty evidence); heart rate (MD -6.30 bpm, 95% CI -16.04 to 3.44; 1 study, 40 infants; low-certainty evidence); or oxygen saturation during endotracheal suctioning (MD -0.80, 95% CI -4.82 to 3.22; 1 study, 40 infants; low-certainty evidence). No studies reported SRB, SDB or IVH. White noise (one study) White noise during endotracheal suctioning probably has little or no effect on PIPP (MD -0.65, 95% CI -2.51 to 1.21; 1 study, 40 infants; low-certainty evidence); heart rate (MD -1.85 bpm, 95% CI -11.46 to 7.76; 1 study, 40 infants; low-certainty evidence); or oxygen saturation (MD 2.25, 95% CI -2.03 to 6.53; 1 study, 40 infants; low-certainty evidence). No studies reported SRB, SDB or IVH. Facilitated tucking / four-handed care / gentle human touch probably reduces PIPP score. The evidence of a single study suggests that facilitated tucking / four-handed care / gentle human touch slightly increases self-regulatory and approach behaviours during endotracheal suctioning. Based on a single study, familiar odour and white noise have little or no effect on any of the outcomes compared to no intervention. The use of expressed breast milk or oral sucrose suggests that there is no discernible advantage of one method over the other for reducing pain during endotracheal suctioning. None of the studies reported on any of the prespecified secondary outcomes of adverse events.

Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.

Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015. To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC. We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics. We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD. We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons. Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

RRab variables with identical light-curve shapes at different pulsation periods

ABSTRACT In this paper, we report on the detection of RRab stars with quasi-identical-shape light curves but period differences as large as 0.05–0.21 d using the Galactic bulge data of the OGLE-IV survey. We have examined stars with shorter periods than the Oosterhoff I ridge of the bulge. These stars generally have smaller amplitudes and larger Fourier phase-differences than the typical bulge RRab stars have at the same period. Many of these ‘anomalous’ stars have good-quality light curves without any sign of the Blazhko modulation. Examining their Fourier parameters revealed that several of these stars show very similar light curve to the typical bulge RR Lyrae. We found hundreds of quasi-identical-shape light-curve pairs with different periods between the ‘anomalous’- and the ‘normal’-position RRab stars based on the OGLE I-band data. The OGLE V-band, and the archive VVV and MACHO surveys Ks-, b- and r-band data of these stars were also checked for light-curve-shape similarity. Finally, 149 pairs with identical-shape light curves in each available photometric band were identified. Calculating the physical properties of the variables using empirical formulae, on average, −0.5 dex, −0.13 mag, 0.67, and 165 K differences between the [Fe/H], MV, R/R⊙, and Teff values of the members of the pairs are derived, being the short-period stars less metal-poor, fainter, smaller, and hotter than the long-period variables. To explain the existence of variables with different physical properties and pulsation periods but with identical-shape light curves is a challenging task for modelling.

New distance estimates to Pulsating RR Lyrae Star DM And.

This is a study of the photometric data of the RR Lyrae star, DM And, in the B, V, sdssi, and sdss-z filters. The light curve shapes and estimated period 0.631± 0.011d in the B-filter, 0.631± 0.012d in the V-filter, 0.631± 0.011d in the sdss-i filter, 0.631± 0.011d in the sdss-z filter, and an average period of 0.6301 0.011d represent that of a typical RRab type RR Lyrae star. DM And’s magnitude is 12.175± 0.010 in B, 11.70± 0.010 in V, 11.60± 0.03 in sdss-i and 11.475± 0.046 in sdss-z, with an average magnitude of 11.738± 0.024. DM And has a measured distance averaged over all filters of 1647± 42 pc, 1558± 46 pc in V, 1728± 77 pc in sdss-i, and 1653± 95 pc in sdss-z. These results are comparable to GAIA’s measured distance of 1572± 157 pc.

Short versus long feeding interval for bolus feedings in very preterm infants.

There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract. To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding. We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention. We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference). We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay. The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.

Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates.

Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates.

Highly photocatalytic activity of natural halloysite - based material for the treatment of dyes in wastewater

In this study, the halloysite nanotube material will be fabricated from a natural halloysite mineral and used as a support for the photocatalytic activity phase based on TiO2. The material is characterized by modern physicochemical methods such as XRD, SEM, BET, UV - vis spectrum, and EDX. Accordingly, the refined halloysite has a nanoscale with a length of about 1.3 μm and a capillary size of about 5 nm. After the deposition of Ag - TiO2 on the halloysite, the specific surface of the material measured by the BET method was about 60 m2/g, and the structure of the halloysite was intact. The band - gap energy of as - prepared materials is also significantly improved in comparison to pure TiO2, makes the material capable of absorbing longer wavelengths of light in the photocatalytic process. The Photocatalyst based on Halloysite and TiO2 showed very high efficiency, up to more than 95% in the decomposition of typical organic pollutant RR - 195. This result shows great potential in this novel material in environmental treatment applications.

Non-pharmacological care for opioid withdrawal in newborns.

Non-pharmacological care for opioid withdrawal in newborns.

Continuous glucose monitoring for the prevention of morbidity and mortality in preterm infants.

Preterm infantsare susceptible tohyperglycemia andhypoglycemia, conditions which may lead to adverse neurodevelopment. The use of continuous glucose monitoring devices(CGM) might help keeping glucose levels in the normal range, and reduce the need for blood sampling. However, the useof CGM might be associated with harms in the preterm infant. Objective one: to assess the benefits and harms of CGM alone versus standard method of glycemic measure in preterm infants. Objective two: to assess the benefits and harms of CGM with automated algorithm versus standard method of glycemic measure in preterm infants. Objective three: to assess the benefits and harms of CGM with automated algorithm versus CGM without automated algorithm in preterm infants. We adopted the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 25September 2020); Embase (1980 to 25September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 25September 2020). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Randomized controlled trials (RCTs) and quasi-RCTs in preterm infants comparing: 1)the use ofCGMversus intermittent modalities to measure glycemia (comparison 1); orCGM associated with prespecified interventions to correct hypoglycemiaor hyperglycemia versus CGM without such prespecified interventions(comparison 2). We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of the evidence. Four trials enrolling 138 infants met our inclusion criteria. Investigators in three trials (118 infants) comparedthe use ofCGM to intermittent modalities (comparison one); however one of these trialswas analyzedseparately because CGMwas used as a standalone device, without being coupled to a control algorithm like in the other trials. A fourth trial (20infants) assessed CGM with an automated algorithm versus CGM with a manual algorithm. None of the four included trials reported the neurodevelopmental outcome, i.e. the primary outcome of this review. Within comparison one, the certainty of the evidence on the use of CGM on mortality during hospitalization is very uncertain (typical RR 3.00,95% CI 0.13 to70.30; typical RD 0.04, 95% CI -0.06to 0.14; 50 participants; 1 study; very low certainty). The number of hypoglycemic episodes was reported in two studies with conflicting data. The number of hyperglycemic episodes was reported in one study(typical MD -1.40,95% CI -2.84to 0.04; 50 participants; 1 study). The certaintyof the evidence was very low for all outcomesbecause of limitations in study design, and imprecision of estimates. Threestudiesareongoing. There is insufficient evidence to determine if CGM improves preterm infant mortality or morbidities. Long-term outcomeswerenot reported. Clinical trials are required to determine the most effective CGM and glycemic management regimens in preterm infants before larger studies can be performed to assess the efficacy of CGMfor reducing mortality, morbidity and long-term neurodevelopmental impairments.The absence of CGM labelled for neonatal use is still a major limit in its use as well as the absence of dedicated neonatal devices.

Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants.

Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants.

Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants.

Respiratory distress, particularly respiratory distress syndrome (RDS), is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant has been the usual treatment, but it is invasive, potentially resulting in airway and lung injury. Continuous positive airway pressure (CPAP) has been used for the prevention and treatment of respiratory distress, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae. To determine the effect of continuous distending pressure in the form of CPAP on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress. We used the standard strategy of Cochrane Neonatal to search CENTRAL (2020, Issue 6); Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. All randomised or quasi-randomised trials of preterm infants with respiratory distress were eligible. Interventions were CPAP by mask, nasal prong, nasopharyngeal tube or endotracheal tube, compared with spontaneous breathing with supplemental oxygen as necessary. We used standard methods of Cochrane and its Neonatal Review Group, including independent assessment of risk of bias and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence. Subgroup analyses were planned on the basis of birth weight (greater than or less than 1000 g or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), timing of application (early versus late in the course of respiratory distress), pressure applied (high versus low) and trial setting (tertiary compared with non-tertiary hospitals; high income compared with low income) MAIN RESULTS: We included five studies involving 322 infants; two studies used face mask CPAP, two studies used nasal CPAP and one study used endotracheal CPAP and continuing negative pressure for a small number of less ill babies. For this update, we included one new trial. CPAP was associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.64, 95% confidence interval (CI) 0.50 to 0.82; typical risk difference (RD) -0.19, 95% CI -0.28 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 4 to 11; I2 = 50%; 5 studies, 322 infants; very low-certainty evidence), lower use of ventilatory assistance (typical RR 0.72, 95% CI 0.54 to 0.96; typical RD -0.13, 95% CI -0.25 to -0.02; NNTB 8, 95% CI 4 to 50; I2 = 55%; very low-certainty evidence) and lower overall mortality (typical RR 0.53, 95% CI 0.34 to 0.83; typical RD -0.11, 95% CI -0.18 to -0.04; NNTB 9, 95% CI 2 to 13; I2 = 0%; 5 studies, 322 infants; moderate-certainty evidence). CPAP was associated with increased risk of pneumothorax (typical RR 2.48, 95% CI 1.16 to 5.30; typical RD 0.09, 95% CI 0.02 to 0.16; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 7 to 50; I2 = 0%; 4 studies, 274 infants; low-certainty evidence). There was no evidence of a difference in bronchopulmonary dysplasia, defined as oxygen dependency at 28 days (RR 1.04, 95% CI 0.35 to 3.13; I2 = 0%; 2 studies, 209 infants; very low-certainty evidence). The trials did not report use of surfactant, intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis and neurodevelopment outcomes in childhood. In preterm infants with respiratory distress, the application of CPAP is associated with reduced respiratory failure, use of mechanical ventilation and mortality and an increased rate of pneumothorax compared to spontaneous breathing with supplemental oxygen as necessary. Three out of five of these trials were conducted in the 1970s. Therefore, the applicability of these results to current practice is unclear. Further studies in resource-poor settings should be considered and research to determine the most appropriate pressure level needs to be considered.

Early versus delayed continuous positive airway pressure (CPAP) for respiratory distress in preterm infants.

The application of continuous positive airway pressure (CPAP) has been shown to have some benefits in the treatment of preterm infants with respiratory distress. CPAP has the potential to reduce lung damage, particularly if applied early before atelectasis has occurred. Early application may better conserve an infant's own surfactant stores and consequently may be more effective than later application. • 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. We included trials that used random or quasi-random allocation to either early or delayed CPAP for spontaneously breathing preterm infants in respiratory distress. 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. 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. 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.

Head midline position for preventing the occurrence or extension of germinal matrix-intraventricular haemorrhage in preterm infants.

Head position during care may affect cerebral haemodynamics and contribute to the development of germinal matrix-intraventricular haemorrhage (GM-IVH) in very preterm infants. Turning the head toward one side may occlude jugular venous drainage while increasing intracranial pressure and cerebral blood volume. It is suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the infant is cared for in the supine 'head midline' position. To assess whether head midline position is more effective than other head positions for preventing (or preventing extension) of GM-IVH in very preterm infants (< 32 weeks' gestation at birth). We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 12 September 2019), Embase (1980 to 12 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 12 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles. Randomised controlled trials (RCTs) comparing caring for very preterm infants in a supine head midline position versus a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of haemorrhage in a subgroup of infants. We planned to analyse horizontal (flat) versus head elevated positions separately for all body positions. We used standard methods of Cochrane Neonatal. For each of the included trials, two review authors independently extracted data and assessed risk of bias. The primary outcomes were GM-IVH, severe IVH, and neonatal death. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence. Three RCTs, with a total of 290 infants (either < 30 weeks' gestational age or < 1000 g body weight), met the inclusion criteria. Two trials compared supine midline head position versus head rotated 90° with the cot flat. One trial compared supine midline head position versus head rotated 90° with the bed tilted at 30°. We found no trials that compared supine versus prone midline head position. Meta-analysis of three trials (290 infants) did not show an effect on rates of GM-IVH (RR 1.11, 95% confidence interval (CI) 0.78 to 1.56; I² = 0%) and severe IVH (RR 0.71, 95% CI 0.37 to 1.33; I² = 0%). Neonatal mortality (RR 0.49, 95% CI 0.25 to 0.93; I² = 0%; RD -0.09, 95% CI -0.16 to -0.01) and mortality until hospital discharge (typical RR 0.50, 95% CI 0.28 to 0.90; I² = 0%; RD -0.10, 95% CI -0.18 to -0.02) were lower in the supine midline head position. The certainty of the evidence was very low for all outcomes because of limitations in study design and imprecision of estimates. We identified one ongoing study. We found few trial data on the effects of head midline position on GM-IVH in very preterm infants. Although meta-analyses suggest that mortality might be reduced, the certainty of the evidence is very low and it is unclear whether any effect is due to cot tilting (a co-intervention in one trial). Further high-quality RCTs would be needed to resolve this uncertainty.

Multi-nutrient fortification of human milk for preterm infants.

Human breast milk-fed preterm infants can accumulate nutrient deficits leading to extrauterine growth restriction. Feeding preterm infants with multi-nutrient fortified human milk could increase nutrient accretion and growth rates and improve neurodevelopmental outcomes. Concern exists, however, that multi-nutrient fortifiers are associated with adverse events such as feed intolerance and necrotising enterocolitis. To determine whether multi-nutrient fortified human milk, compared with unfortified human milk, affects important outcomes (including growth rate and neurodevelopment) of preterm infants without increasing the risk of adverse effects (such as feed intolerance and necrotising enterocolitis). We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 26 September 2019), Embase (1980 to 26 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 26 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised controlled trials that compared feeding preterm infants with multi-nutrient (protein and energy plus minerals, vitamins, or other nutrients) fortified human breast milk versus unfortified (no added protein or energy) breast milk. We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RRs), risk differences, and mean differences (MDs). We assessed the certainty of the body of evidence at the outcome level using "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) methods. We identified 18 trials in which a total of 1456 preterm infants participated. These trials were generally small and methodologically weak. Meta-analyses provided low- to moderate-certainty evidence showing that multi-nutrient fortification of human milk increases in-hospital rate of weight gain (MD 1.76 g/kg/d, 95% confidence interval (CI) 1.30 to 2.22), body length (MD 0.11 cm/week, 95% CI 0.08 to 0.15), or head circumference (MD 0.06 cm/week, 95% CI 0.03 to 0.08) among preterm infants. Few data on growth and developmental outcomes assessed beyond infancy are available, and these do not show effects of multi-nutrient fortification. The data do not suggest other benefits or harms and provide low-certainty evidence suggesting effects of multi-nutrient fortification on the risk of necrotising enterocolitis in preterm infants (typical RR 1.37, 95% CI 0.72 to 2.63; 13 studies, 1110 infants). Feeding preterm infants with multi-nutrient fortified human breast milk compared with unfortified human breast milk is associated with modest increases in in-hospital growth rates. Evidence is insufficient to show whether multi-nutrient fortification has any effect on long-term growth or neurodevelopment.

Parameters Analysis of Sample Entropy, Permutation Entropy and Permutation Ratio Entropy for RR Interval Time Series

Proper parameters can improve performance of entropy methods for discerning electrocardiogram (ECG) signals. So, we tried to determine proper parameters of three entropy methods i.e., a novel permutation ratio entropy (PRE), sample entropy (SmpE) and permutation entropy (PE) for discerning several typical ECG RR interval recordings i.e., normal sinus rhythm (NSR), congestive heart failure (CHF) and NSR and arrhythmia RR (ARR) interval recordings. The three entropy methods were first calculated for a logistic sequence to evaluate their sensitivity to dynamic property changes within a time series. Their capabilities of distinguishing complexity between NSR and CHF, NSR and ARR, and CHF and ARR RR interval recordings were compared. Statistical differences between the three entropy values for normal (i.e., NSR) and abnormal RR interval recordings (i.e., CHF and ARR) were analysed respectively. Performance of the entropy methods in simultaneously discerning the three groups (i.e., NSR, CHF and ARR groups) were also compared. PRE more accurately reflected logistic sequence changes from period doublings to chaos than SmpE or PE did. In experiments with real data, PRE correctly yielded higher values on NSR RR recordings than on CHF and ARR recordings and exhibited significant differences (p < 0.01) on more parameter pairs than SmpE and PE did.

Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.

Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later. We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates. We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence. Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies. We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes.

Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. To assess the effectiveness and safety of early versus late initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight (LBW) infants. The standard search of the Cochrane Neonatal Review Group (CNRG) was performed in 2006 and updated in 2009. Updated search in September 2009 as follows: The Cochrane Library, MEDLINE (search via PubMed), CINAHL and EMBASE were searched from 2005 to September 2009. The searches were repeated in March 2012. The Pediatric Academic Societies' Annual meetings were searched electronically from 2000 to 2012 at Abstracts2ViewTM as were clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp). Randomised or quasi-randomised controlled trials enrolling preterm or LBW infants less than eight days of age. Early initiation of EPO (initiated at less than eight days of age) versus late initiation of EPO (initiated at eight to 28 days of age). The standard methods of the CNRG were followed. Weighted treatment effects included typical risk ratio (RR), typical risk difference (RD), number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) and mean difference (MD), all with 95% confidence intervals (CI). A fixed-effect model was used for meta-analyses and heterogeneity was evaluated using the I-squared (I2) test. No new trials were identified in March of 2012. Two high quality randomised double-blind controlled studies enrolling 262 infants were identified. A non-significant reduction in the 'Use of one or more RBC transfusions' [two studies 262 infants; typical RR 0.91 (95% CI 0.78 to 1.06); typical RD -0.07 (95% CI -0.18 to 0.04; I2 = 0% for both RR and RD] favouring early EPO was noted. Early EPO administration resulted in a non-significant reduction in the "number of transfusions per infant" compared with late EPO [typical MD - 0.32 (95% CI -0.92 to 0.29)]. There was no significant reduction in total volume of blood transfused per infant or in the number of donors to whom the infant was exposed. Early EPO led to a significant increase in the risk of retinopathy of prematurity (ROP) (all stages) [two studies, 191 infants; typical RR 1.40 (95% CI 1.05 to 1.86); typical RD 0.16 (95% CI 0.03 to 0.29); NNTH 6 (95% CI 3 to 33)]. There was high heterogeneity for this outcome (I2 = 86% for RR and 81% for RD). Both studies (191 infants) reported on ROP stage > 3. No statistically significant increase in risk was noted [typical RR 1.56 (95% CI 0.71 to 3.41); typical RD 0.05 (-0.04 to 0.14)] There was no heterogeneity for this outcome (0% for both RR and RD). No other important favourable or adverse neonatal outcomes or side effects were reported. The use of early EPO did not significantly reduce the 'Use of one or more RBC transfusions' or the 'Number of transfusions per infant" compared with late EPO administration. The finding of a statistically significant increased risk of ROP (any grade) and a similar trend for ROP stage > 3 with early EPO treatment is of great concern.

Early erythropoiesis-stimulating agents in preterm or low birth weight infants.

Early erythropoiesis-stimulating agents in preterm or low birth weight infants.

Intravenous immunoglobulin for suspected or proven infection in neonates.

Neonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG. To assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection. For this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied. Randomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up. Statistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), all with 95% confidence intervals (CIs), and the I2 statistic to examine for statistical heterogeneity. The updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I2 = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09; RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1446); RR 0.95, 95% CI 0.74 to 1.21; RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1393); RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected or proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I2 = 17% for RR and 53% for RD). The undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants with suspected or proven infection. Although based on a small sample size (n = 266), this update provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection. Routine administration of IVIG or IgM-enriched IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. No further research is recommended.