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Archives of Disease in Childhood. Fetal... Jul 2020To determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3)... (Meta-Analysis)
Meta-Analysis
AIM
To determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found in babies with NEC.
METHODS
Systematic review: three independent investigators searched for studies reporting infants with NDI and a history of NEC (PubMed, Medline, Cochrane Collaboration, Scopus). Meta-analysis: using RevMan V.5.3, we compared NDI incidence and type of cerebral lesions between NEC infants versus preterm infants and infants with medical vs surgical NEC.
RESULTS
Of 10 674 abstracts screened, 203 full-text articles were examined. In 31 studies (n=2403 infants with NEC), NDI incidence was 40% (IQR 28%-64%) and was higher in infants with surgically treated NEC (43%) compared with medically managed NEC (27%, p<0.00001). The most common NDI in NEC was cerebral palsy (18%). Cerebral lesions: intraventricular haemorrhage (IVH) was more common in NEC babies (26%) compared with preterm infants (18%; p<0.0001). There was no difference in IVH incidence between infants with surgical NEC (25%) and those treated medically (20%; p=0.4). The incidence of periventricular leukomalacia (PVL) was significantly increased in infants with NEC (11%) compared with preterm infants (5%; p<0.00001).
CONCLUSIONS
This study shows that a large proportion of NEC survivors has NDI. NEC babies are at higher risk of developing IVH and/or PVL than babies with prematurity alone. The degree of NDI seems to correlate to the severity of gut damage, with a worse status in infants with surgical NEC compared with those with medical NEC.
TRIAL REGISTRATION NUMBER
CRD42019120522.
Topics: Cerebellum; Enterocolitis, Necrotizing; Humans; Incidence; Infant, Newborn; Neurodevelopmental Disorders
PubMed: 31801792
DOI: 10.1136/archdischild-2019-317830 -
The Cochrane Database of Systematic... Jul 2017Preterm birth is known to constitute the major risk factor for development of germinal matrix-intraventricular hemorrhage (GM-IVH). Head position may affect cerebral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth is known to constitute the major risk factor for development of germinal matrix-intraventricular hemorrhage (GM-IVH). Head position may affect cerebral hemodynamics and thus may be involved indirectly in development of GM-IVH. Turning the head toward one side may functionally occlude jugular venous drainage on the ipsilateral side while increasing intracranial pressure and cerebral blood volume. Thus, it has been suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the patient is in supine midline position with the bed tilted 30°. The midline position might be achieved in the supine position and, with the use of physical aids, in the lateral position as well. Midline position should be kept, at least when the incidence of GM-IVH is greatest, that is, during the first two to three days of life.
OBJECTIVES
Primary objective To assess whether head midline position is more effective than any other head position for preventing or extending germinal matrix-intraventricular hemorrhage in infants born at ≤ 32 weeks' gestational age. Secondary objectives To perform subgroup analyses regarding gestational age, birth weight, intubated versus not intubated, and with or without GM-IVH at trial entry.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to September 19, 2016), Embase (1980 to September 19,.2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to September 19, 2016). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
Randomized clinical controlled trials, quasi-randomized trials, and cluster-randomized controlled trials comparing placing very preterm infants in a head midline position versus placing them in 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 hemorrhage in a subgroup of infants. We planned to analyze horizontal (flat) versus head elevated positions separately for all body positions.
DATA COLLECTION AND ANALYSIS
We used standard methods of the Cochrane Neonatal Review Group. For each of the included trials, two review authors independently extracted data (e.g., number of participants, birth weight, gestational age, initiation and duration of head midline position, co-intervention with horizontal vs head elevated position, use of physical aids to maintain head position) and assessed risk of bias (e.g., adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review are GM-IVH , severe IVH, and neonatal death.
MAIN RESULTS
Our search strategy yielded 2696 references. Two review authors independently assessed all references for inclusion. Two randomized controlled trials, for a total of 110 infants, met the inclusion criteria of this review. Both trials compared supine midline head position with the bed at 0° versus supine head rotated 90° with the bed at 0°. We found no trials that compared supine versus prone midline head position, and no trials that compared effects of head tilting. We found no significant differences in rates of GM-IVH (typical risk ratio [RR] 1.14, 95% confidence interval [CI] 0.55 to 2.35; typical risk difference [RD] 0.03, 95% CI -0.13 to 0.18; two studies, 110 infants; I = 0% for RR and I = 0% for RD), severe IVH (typical RR 1.57, 95% CI 0.28 to 8.98; typical RD 0.02, 95% CI -0.06 to 0.10; two studies, 110 infants; I = 0% for RR and I = 0% for RD), and neonatal mortality (typical RR 0.52, 95% CI 0.16 to 1.65; typical RD -0.07, 95% CI -0.18 to 0.05; two studies, 110 infants; I = 28% for RR and I = 44% for RD). Among secondary outcomes, we found no significant differences in terms of cystic periventricular leukomalacia (one study; RR 3.25, 95% CI 0.14 to 76.01; RD 0.04, 95% CI -0.07 to 0.15), retinopathy of prematurity (one study; RR 2.27, 95% CI 0.85 to 6.11; RD 0.25, 95% CI -0.02 to 0.53), and severe retinopathy of prematurity (one study; RR 2.73, 95% CI 0.31 to 24.14; RD 0.09, 95% CI -0.09 to 0.26). None of the included trials reported on the other specified outcomes of this review (i.e., cerebellar hemorrhage, brain magnetic resonance imaging abnormalities, impairment in cerebral hemodynamics, long-term neurodevelopmental outcomes, and major neurodevelopmental disability). The quality of evidence supporting these findings is limited owing to the imprecision of the estimates. We identified no ongoing studies.
AUTHORS' CONCLUSIONS
Given the imprecision of the estimate, results of this systematic review are consistent with beneficial or detrimental effects of a supine head midline position versus a lateral position and do not provide a definitive answer to the review question.
Topics: Beds; Cerebral Hemorrhage; Cerebral Ventricles; Cerebrovascular Circulation; Head; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Patient Positioning; Publication Bias; Randomized Controlled Trials as Topic; Supine Position
PubMed: 28727900
DOI: 10.1002/14651858.CD012362.pub2 -
The Cochrane Database of Systematic... Mar 2015Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease. A newer form of ventilation called high frequency oscillatory ventilation has been shown in experimental studies to result in less lung injury.
OBJECTIVES
The objective of this review was to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) on the incidence of chronic lung disease (CLD), mortality and other complications associated with prematurity and assisted ventilation in preterm infants who were mechanically ventilated for respiratory distress syndrome (RDS).
SEARCH METHODS
Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings; and from expert informants and handsearching of journals by The Cochrane Collaboration, mainly in the English language. The search was updated in January 2009 and again in November 2014.
SELECTION CRITERIA
Randomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who required assisted ventilation. Randomisation and commencement of treatment needed to be as soon as possible after the start of CV and usually in the first 12 hours of life.
DATA COLLECTION AND ANALYSIS
The methodological quality of each trial was independently reviewed by the review authors. The standard effect measures were relative risk (RR) and risk difference (RD). From 1/RD the number needed to benefit (NNTB) to produce one outcome was calculated. For all measures of effect, 95% confidence intervals (CIs) were used. For interpretation of subgroup analyses, a P value for subgroup differences as well as the I(2) statistic for between-subgroup heterogeneity were calculated. Meta-analysis was performed using both a fixed-effect and a random-effects model. Where heterogeneity was over 50%, the random-effects model RR was also reported.
MAIN RESULTS
Nineteen eligible studies involving 4096 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 to 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The risk of CLD in survivors at term equivalent gestational age was significantly reduced with the use of HFOV but this effect was inconsistent across studies, even after the meta-analysis was restricted to studies that applied a high lung volume strategy with HFOV. Subgroup analysis by HFOV strategy showed a similar effect in trials with a more strict lung volume recruitment strategy, targeting a very low fraction of inspired oxygen (FiO2), and trials with a less strict lung volume recruitment strategy and with a somewhat higher or unspecified target FiO2. Subgroup analyses by age at randomisation, routine surfactant use or not, type of high frequency ventilator (oscillator versus flow interrupter), inspiratory to expiratory (I:E) ratio of high frequency ventilator (1:1 versus 1:2) and CV strategy (lung protective or not) could not sufficiently explain the heterogeneity. Pulmonary air leaks, defined as gross air leaks or pulmonary interstitial emphysema, occurred more frequently in the HFOV group, whereas the risk of severe retinopathy of prematurity was significantly reduced.Although in some studies an increased risk of severe grade intracranial haemorrhage and periventricular leukomalacia was found, the overall meta-analysis revealed no significant differences in effect between HFOV and CV. The short-term neurological morbidity with HFOV was only found in the subgroup of two trials not using a high volume strategy with HFOV. Most trials did not find a significant difference in long-term neurodevelopmental outcome, although one recent trial showed a significant reduction in the risk of cerebral palsy and poor mental development.
AUTHORS' CONCLUSIONS
There is evidence that the use of elective HFOV compared with CV results in a small reduction in the risk of CLD, but the evidence is weakened by the inconsistency of this effect across trials. Probably many factors, both related to the intervention itself as well as to the individual patient, interact in complex ways. In addition, the benefit could be counteracted by an increased risk of acute air leak. Adverse effects on short-term neurological outcomes have been observed in some studies but these effects are not significant overall. Most trials reporting long-term outcome have not identified any difference.
Topics: Chronic Disease; High-Frequency Ventilation; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Lung Injury; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn
PubMed: 25785789
DOI: 10.1002/14651858.CD000104.pub4 -
Ultrasound in Obstetrics & Gynecology :... Nov 2017To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern... (Meta-Analysis)
Meta-Analysis Review
Outcome of monochorionic twin pregnancy with selective intrauterine growth restriction according to umbilical artery Doppler flow pattern of smaller twin: systematic review and meta-analysis.
OBJECTIVE
To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern of the smaller twin.
METHODS
An electronic search of MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases (2000-2016) was performed. sIUGR was defined as the presence of one twin with an estimated fetal weight and/or abdominal circumference < 10 or < 5 percentile and classified according to the umbilical artery Doppler flow pattern of the smaller twin (Type I: persistently positive; Type II: persistently absent/reversed; Type III: intermittently absent/reversed). Primary outcomes were perinatal mortality, intrauterine death, neonatal death and double fetal loss. Secondary outcomes were neonatal morbidity, including abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, admission to neonatal intensive care unit and respiratory distress syndrome, deterioration of fetal status, gestational age at delivery and degree of birth-weight discordance. A composite adverse outcome, defined as the presence of any mortality or abnormal brain findings, was also assessed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was used to compute the summary odds ratios (ORs), mean differences (MD) and proportions for the different outcomes.
RESULTS
Thirteen studies (610 pregnancies) were included. The risk of perinatal mortality was higher in twins affected by Type II compared with Type I sIUGR (OR, 4.1 (95% CI, 1.6-10.3)), whereas there was no difference among the other variants of growth restriction. Risk of abnormal postnatal brain imaging was significantly higher in twins affected by either Type II (OR, 4.9 (95% CI, 1.9-12.9)) or Type III (OR, 8.2 (95% CI, 2.0-33.1)) sIUGR compared with Type I sIUGR. The risk for neonatal intensive care unit admission was higher in Type II compared with Type I sIUGR (OR, 18.3 (95% CI, 1.0-339.7)). Twin pregnancies affected by Type I sIUGR were delivered at a significantly later gestational age compared with Type II (MD, 2.8 (95% CI, 1.83-3.86) weeks) and Type III (MD, 2.1 (95% CI, 0.97-3.19) weeks). The degree of birth-weight discordance was higher in Type II compared with Type I (MD, 21.6% (95% CI, 9.9-33.2%)) and Type III (MD, 9.3% (95% CI, 3.8-14.9%)) sIUGR.
CONCLUSION
Monochorionic twin pregnancies affected by Type II sIUGR are at a higher risk of perinatal mortality and morbidity compared with Type I. The likelihood of an abnormal outcome is usually not significantly different between sIUGR Types II and III, although the latter has an unpredictable clinical course. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Birth Weight; Diseases in Twins; Female; Fetal Death; Fetal Growth Retardation; Fetal Weight; Gestational Age; Humans; Infant, Newborn; Perinatal Mortality; Pregnancy; Pregnancy Outcome; Pregnancy, Twin; Twins, Monozygotic; Ultrasonography, Doppler; Ultrasonography, Prenatal; Umbilical Arteries
PubMed: 27859836
DOI: 10.1002/uog.17362 -
The Cochrane Database of Systematic... May 2018Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO - proportion of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO - proportion of the breathed air that is oxygen) targeted to oxygen saturation (SpO - an estimate of the amount of oxygen in the blood) for infants born preterm is unclear.
OBJECTIVES
To determine whether lower or higher initial oxygen concentrations, when titrated according to oxygen saturation targets during the resuscitation of preterm infants at birth, lead to improved short- and long-term mortality and morbidity.
SEARCH METHODS
We conducted electronic searches of the Cochrane Central Register of Controlled Trials (13 October 2017), Ovid MEDLINE (1946 to 13 October 2017), Embase (1974 to 13 October 2017) and CINAHL (1982 to 13 October 2017); we also searched previous reviews (including cross-references), contacted expert informants, and handsearched journals.
SELECTION CRITERIA
We included randomised controlled trials (including cluster- and quasi-randomised trials) which enrolled preterm infants requiring resuscitation following birth and allocated them to receive either lower (FiO < 0.4) or higher (FiO ≥ 0.4) initial oxygen concentrations titrated to target oxygen saturation.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. Primary outcomes included mortality near term or at discharge (latest reported) and neurodevelopmental disability. We conducted meta-analysis using a fixed-effect model. We assessed the quality of the evidence using GRADE.
MAIN RESULTS
The search identified 10 eligible trials. Meta-analysis of the 10 included studies (914 infants) showed no difference in mortality to discharge between lower (FiO < 0.4) and higher (FiO ≥ 0.4) initial oxygen concentrations targeted to oxygen saturation (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.68 to 1.63). We identified no heterogeneity in this analysis. We graded the quality of the evidence as low due to risk of bias and imprecision. There were no significant subgroup effects according to inspired oxygen concentration strata (FiO 0.21 versus ≥ 0.4 to < 0.6; FiO 0.21 versus ≥ 0.6 to 1.0; and FiO ≥ 0.3 to < 0.4 versus ≥ 0.6 to 1.0). Subgroup analysis identified a single trial that reported increased mortality from use of lower (FiO 0.21) versus higher (FiO 1.0) initial oxygen concentration targeted to a lowest SpO of less than 85%, whereas meta-analysis of nine trials targeting a lowest SpO of 85% to 90% found no difference in mortality.Meta-analysis of two trials (208 infants) showed no difference in neurodevelopmental disability at 24 months between infants receiving lower (FiO < 0.4) versus higher (FiO > 0.4) initial oxygen concentrations targeted to oxygen saturation. Other outcomes were incompletely reported by studies. Overall, we found no difference in use of intermittent positive pressure ventilation or intubation in the delivery room; retinopathy (damage to the retina of the eyes, measured as any retinopathy and severe retinopathy); intraventricular haemorrhage (any and severe); periventricular leukomalacia (a type of white-matter brain injury); necrotising enterocolitis (a condition where a portion of the bowel dies); chronic lung disease at 36 weeks' gestation; mortality to follow up; postnatal growth failure; and patent ductus arteriosus. We graded the quality of the evidence for these outcomes as low or very low.
AUTHORS' CONCLUSIONS
There is uncertainty as to whether initiating post birth resuscitation in preterm infants using lower (FiO < 0.4) or higher (FiO ≥ 0.4) oxygen concentrations, targeted to oxygen saturations in the first 10 minutes, has an important effect on mortality or major morbidity, intubation during post birth resuscitation, other resuscitation outcomes, and long-term outcomes including neurodevelopmental disability. We assessed the quality of the evidence for all outcomes as low to very low. Further large, well designed trials are needed to assess the effect of using different initial oxygen concentrations and the effect of targeting different oxygen saturations.
Topics: Cerebral Hemorrhage; Child, Preschool; Enterocolitis, Necrotizing; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Lung Diseases; Neurodevelopmental Disorders; Oxygen; Randomized Controlled Trials as Topic; Resuscitation; Retinopathy of Prematurity
PubMed: 29726010
DOI: 10.1002/14651858.CD010239.pub2 -
The Cochrane Database of Systematic... Jan 2015Infants in the neonatal intensive care unit (NICU) are subjected to stress, including sound of high intensity. The sound environment in the NICU is louder than most home... (Review)
Review
BACKGROUND
Infants in the neonatal intensive care unit (NICU) are subjected to stress, including sound of high intensity. The sound environment in the NICU is louder than most home or office environments and contains disturbing noises of short duration and at irregular intervals. There are competing auditory signals that frequently challenge preterm infants, staff and parents. The sound levels in NICUs often exceed the maximum acceptable level of 45 decibels (dB), recommended by the American Academy of Pediatrics. Hearing impairment is diagnosed in 2% to 10% of preterm infants versus 0.1% of the general paediatric population. Noise may cause apnoea, hypoxaemia, alternation in oxygen saturation, and increased oxygen consumption secondary to elevated heart and respiratory rates and may, therefore, decrease the amount of calories available for growth. Elevated levels of speech are needed to overcome the noisy environment in the NICU, thereby increasing the negative impacts on staff, newborns, and their families. High noise levels are associated with an increased rate of errors and accidents, leading to decreased performance among staff. The aim of interventions included in this review is to reduce sound levels to 45 dB or less. This can be achieved by lowering the sound levels in an entire unit, treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled, or reducing the sound levels that reaches the individual infant by using earmuffs or earplugs. By lowering the sound levels that reach the neonate, the resulting stress on the cardiovascular, respiratory, neurological, and endocrine systems can be diminished, thereby promoting growth and reducing adverse neonatal outcomes.
OBJECTIVES
Primary objectiveTo determine the effects of sound reduction on growth and long-term neurodevelopmental outcomes of neonates. Secondary objectives1. To evaluate the effects of sound reduction on short-term medical outcomes (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity).2. To evaluate the effects of sound reduction on sleep patterns at three months of age.3. To evaluate the effects of sound reduction on staff performance.4. To evaluate the effects of sound reduction in the neonatal intensive care unit (NICU) on parents' satisfaction with the care.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings, clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp), Pediatric Academic Societies Annual meetings 2000 to 2014 (Abstracts2View(TM)), reference lists of identified trials, and reviews to November 2014.
SELECTION CRITERIA
Preterm infants (< 32 weeks' postmenstrual age (PMA) or < 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or a stepdown unit.
DATA COLLECTION AND ANALYSIS
We performed data collection and analyses according to the Cochrane Neonatal Review Group.
MAIN RESULTS
One small, high quality study assessing the effects of silicone earplugs versus no earplugs qualified for inclusion. The original inclusion criteria in our protocol stipulated an age of < 48 hours at the time of initiating sound reduction. We made a deviation from our protocol and included this study in which some infants would have been > 48 hours old. There was no significant difference in weight at 34 weeks postmenstrual age (PMA): mean difference (MD) 111 g (95% confidence interval (CI) -151 to 374 g) (n = 23). There was no significant difference in weight at 18 to 22 months corrected age between the groups: MD 0.31 kg, 95% CI -1.53 to 2.16 kg (n = 14). There was a significant difference in Mental Developmental Index (Bayley II) favouring the silicone earplugs group at 18 to 22 months corrected age: MD 14.00, 95% CI 3.13 to 24.87 (n = 12), but not for Psychomotor Development Index (Bayley II) at 18 to 22 months corrected age: MD -2.16, 95% CI -18.44 to 14.12 (n =12).
AUTHORS' CONCLUSIONS
To date, only 34 infants have been enrolled in a randomised controlled trial (RCT) testing the effectiveness of reducing sound levels that reach the infants' ears in the NICU. Based on the small sample size of this single trial, we cannot make any recommendations for clinical practice. Larger, well designed, conducted and reported trials are needed.
Topics: Ear Protective Devices; Employee Performance Appraisal; Health Personnel; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Noise; Parents; Randomized Controlled Trials as Topic; Sound; Stress, Physiological
PubMed: 25633155
DOI: 10.1002/14651858.CD010333.pub2 -
The Cochrane Database of Systematic... Feb 2020Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia and to provide neuro protection and protection against necrotising enterocolitis (NEC). Darbepoetin (Darbe) and EPO are currently available ESAs.
OBJECTIVES
To assess the effectiveness and safety of ESAs (erythropoietin (EPO) and/or Darbe) initiated early (before eight days after birth) compared with placebo or no intervention in reducing red blood cell (RBC) transfusions, adverse neurological outcomes, and feeding intolerance including necrotising enterocolitis (NEC) in preterm and/or low birth weight infants. Primary objective for studies that primarily investigate the effectiveness and safety of ESAs administered early in reducing red blood cell transfusions: To assess the effectiveness and safety of ESAs initiated early in reducing red blood cell transfusions in preterm infants. Secondary objectives: Review authors performed subgroup analyses of low (≤ 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and the amount of iron supplementation provided: none, low (≤ 5 mg/kg/d), and high (> 5 mg/kg/d). Primary objective for studies that primarily investigate the neuro protective effectiveness of ESAs: To assess the effectiveness and safety of ESAs initiated early in reducing adverse neurological outcomes in preterm infants. Primary objective for studies that primarily investigate the effectiveness of EPO or Darbe administered early in reducing feeding intolerance: To assess the effectiveness and safety of ESAs administered early in reducing feeding intolerance (and NEC) in preterm infants. Other secondary objectives: To compare the effectiveness of ESAs in reducing the incidence of adverse events and improving long-term neurodevelopmental outcomes.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE via PubMed (1966 to 10 March 2017), Embase (1980 to 10 March 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 10 March 2017). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised and quasi-randomised controlled trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of early initiation of EAS treatment versus placebo or no intervention in preterm or low birth weight infants.
DATA COLLECTION AND ANALYSIS
We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and the GRADE approach to assess the quality of evidence.
MAIN RESULTS
This updated review includes 34 studies enrolling 3643 infants. All analyses compared ESAs versus a control consisting of placebo or no treatment. Early ESAs reduced the risk of 'use of one or more [red blood cell] RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.74 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I = 69% for RR and 62% for RD (moderate heterogeneity); number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 6 to 10; 19 studies, 1750 infants). The quality of the evidence was low. Necrotising enterocolitis was significantly reduced in the ESA group compared with the placebo group (typical RR 0.69, 95% CI 0.52 to 0.91; typical RD -0.03, 95% CI -0.05 to -0.01; I = 0% for RR and 22% for RD (low heterogeneity); NNTB 33, 95% CI 20 to 100; 15 studies, 2639 infants). The quality of the evidence was moderate. Data show a reduction in 'Any neurodevelopmental impairment at 18 to 22 months' corrected age in the ESA group (typical RR 0.62, 95% CI 0.48 to 0.80; typical RD -0.08, 95% CI -0.12 to -0.04; NNTB 13, 95% CI 8 to 25. I = 76% for RR (high heterogeneity) and 66% for RD (moderate); 4 studies, 1130 infants). The quality of the evidence was low. Results reveal increased scores on the Bayley-II Mental Development Index (MDI) at 18 to 24 months in the ESA group (weighted mean difference (WMD) 8.22, 95% CI 6.52 to 9.92; I = 97% (high heterogeneity); 3 studies, 981 children). The quality of the evidence was low. The total volume of RBCs transfused per infant was reduced by 7 mL/kg. The number of RBC transfusions per infant was minimally reduced, but the number of donors to whom infants who were transfused were exposed was not significantly reduced. Data show no significant difference in risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.24, 95% CI 0.81 to 1.90; typical RD 0.01, 95% CI -0.02 to 0.04; I = 0% (no heterogeneity) for RR; I = 34% (low heterogeneity) for RD; 8 studies, 1283 infants). Mortality was not affected, but results show significant reductions in the incidence of intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL).
AUTHORS' CONCLUSIONS
Early administration of ESAs reduces the use of red blood cell (RBC) transfusions, the volume of RBCs transfused, and donor exposure after study entry. Small reductions are likely to be of limited clinical importance. Donor exposure probably is not avoided, given that all but one study included infants who had received RBC transfusions before trial entry. This update found no significant difference in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age, which has been a topic of concern in earlier versions of this review. Early EPO treatment significantly decreased rates of IVH, PVL, and NEC. Neurodevelopmental outcomes at 18 to 22 months and later varied in published studies. Ongoing research should evaluate current clinical practices that will limit donor exposure. Promising but conflicting results related to the neuro protective effect of early EPO require further study. Very different results from the two largest published trials and high heterogeneity in the analyses indicate that we should wait for the results of two ongoing large trials before drawing firm conclusions. Administration of EPO is not currently recommended because limited benefits have been identified to date. Use of darbepoetin requires further study.
Topics: Anemia, Neonatal; Enterocolitis, Necrotizing; Erythropoiesis; Erythropoietin; Hematinics; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Randomized Controlled Trials as Topic; Retinopathy of Prematurity
PubMed: 32048730
DOI: 10.1002/14651858.CD004863.pub6 -
Current Pediatric Reviews 2020Noise may cause stress responses such as apnea, hypoxemia, changes in oxygen saturation and augmented oxygen consumption secondary to elevated heart and respiratory...
Noise may cause stress responses such as apnea, hypoxemia, changes in oxygen saturation and augmented oxygen consumption secondary to elevated heart and respiratory rates. Moreover, stress results in increased intracranial pressure, abnormal sleep patterns, hearing impairment, and bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, retardate development and alterations in the neuroendocrine system. Herein, this study aimed to discuss the effects of earmuffs on physiological parameters in preterm infants. The relevant and available peer-reviewed publications from 2012 to 2018 from various databases were analyzed. For the assessment of the studies, the full-text accessible studies were included for analysis. The retrieved documents were analyzed using VOSviewer regarding the geographical distributions of the documents with their numbers and citations, keywords proposed by the researchers. All records with the term "earmuffs OR earmuff" in the "article title, abstract, keywords" were retrieved from different databases. Accordingly, 396 documents containing the word "earmuffs OR earmuff" were recorded. The search was then restricted for publications that contain the words "noise AND nursing AND preterm" in the title and abstracts (TITLE-ABS-KEY (earmuffs OR earmuff)) AND (noise AND nursing AND preterm) (Scopus=390; Web of Science=1, Medline=2; Cochrane=1; Embase=1= Pubmed=1=n=396). After inclusion and exclusion criteria, 7 documents were recorded and then evaluated for the present study. As a conclusion, the effects of earmuffs on physiological parameters of preterm infants have not been clearly understood and reported yet. Along with the present documents, it is not clear that the use of earmuffs reduces stress and provides physiological stability in preterm infants born between approximately 28-32 weeks. The studies with a larger sample size are needed for validation of information reported in the articles analyzed herein.
Topics: Ear Protective Devices; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Noise
PubMed: 32056529
DOI: 10.2174/1573396316666200214112347 -
The Cochrane Database of Systematic... Dec 2015The pure soybean oil based lipid emulsions (S-LE) conventionally used for parenteral nutrition (PN) in preterm infants have high polyunsaturated fatty acid (PUFA)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pure soybean oil based lipid emulsions (S-LE) conventionally used for parenteral nutrition (PN) in preterm infants have high polyunsaturated fatty acid (PUFA) content. The newer lipid emulsions (LE) from alternative lipid sources with reduced PUFA content may improve clinical outcomes in preterm infants.
OBJECTIVES
To determine the safety and efficacy of the newer alternative LE compared with the conventional S-LE for PN in preterm infants.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG) to search the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 7), MEDLINE (1946 to 31 July 2015), EMBASE (1947 to 31 July 2015), CINAHL (1982 to 31 July 2015), Web of Science (31 July 2015), conference proceedings, trial registries (clinicaltrials.gov, controlled-trials.com, WHO's ICTRP), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials in preterm infants (< 37 weeks), comparing newer alternative LE with S-LE.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of the CNRG. We assessed the quality of evidence for important outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, in addition to reporting the conventional statistical significance of results.
MAIN RESULTS
Fifteen studies (N = 979 infants) are included in this review. Alternative LE including medium chain triglycerides/long chain triglycerides (MCT/LCT) LE (3 studies; n = 108), MCT-olive-fish-soy oil-LE (MOFS-LE; 7 studies; n = 469), MCT-fish-soy oil-LE (MFS-LE; 1 study; n = 60), olive-soy oil-LE (OS-LE; 7 studies; n = 406), and borage-soy oil-LE (BS-LE; 1 study; n = 34) were compared with S-LE. The different LE were also considered together to compare 'all fish oil containing-LE' versus S-LE (7 studies; n = 499) and 'all alternative LE' versus S-LE (15 studies; n = 979). Some studies had multiple intervention arms and were included in more than one comparison. No study compared pure fish oil-LE or structured-LE to S-LE.The GRADE quality of evidence (GRADE QoE) ranged from 'low' to 'very low.' Evidence came mostly from small single centre studies, many focusing on biochemical aspects as their primary outcomes, with optimal information size not achieved for the important clinical outcomes in any comparison.In the primary outcomes of the review there was a pooled effect towards decreased bronchopulmonary dysplasia (BPD) in OS-LE vs S-LE (4 studies, n = 261) not reaching statistical significance (typical risk ratio (RR) 0.69, 95% confidence interval (CI) 0.46 to 1.04, I² = 32%; typical risk difference (RD) -0.08, 95% CI -0.17 to 0.00, I² = 76%; GRADE QoE: 'very low'). No difference in BPD was observed in any other comparison. There were no statistically significant differences in the primary outcomes of death, growth rate (g/kg/day) or days to regain birth weight in any comparison.Retinopathy of prematurity (ROP) stage 1-2 was reported to be statistically significantly lower in one single centre study (n = 80) in the MOFS-LE group compared with the S-LE group (1/40 vs 12/40, respectively; RR 0.08, 95% CI 0.01 to 0.61; RD -0.27, 95% CI -0.43 to -0.12; number needed to benefit (NNTB) 4, 95% CI 2 to 8). However there were no statistically significant differences in the secondary outcome of ROP ≥ stage 3 in any of the individual studies or in any comparison (GRADE QoE: 'low' to 'very low'). No other study reported on ROP stages 1 and 2 separately.There were no statistically significant differences in the secondary outcomes of sepsis, PN associated liver disease (PNALD)/cholestasis, ventilation duration, necrotising enterocolitis (NEC) ≥ stage 2, jaundice requiring treatment, intraventricular haemorrhage grade III-IV, periventricular leukomalacia (PVL), patent ductus arteriosus (PDA), hypertriglyceridaemia, and hyperglycaemia in any comparison.No study reported on neurodevelopmental outcomes or essential fatty acid deficiency.
AUTHORS' CONCLUSIONS
All lipid emulsions in this review appeared to be safe and were well tolerated in preterm infants. Compared with the pure soy oil based LE, use of MOFS-LE was associated with a decrease in the early stages (1-2) of ROP in one study. However there were no statistically significant differences in clinically important outcomes including death, growth, BPD, sepsis, ROP ≥ stage 3, and PNALD with the use of newer alternative LE versus the conventional pure soy oil based LE (GRADE QoE ranged from 'low' to 'very low'). Currently there is insufficient evidence to recommend any alternative LE over S-LE or vice versa in preterm infants.Larger randomised studies focusing on important clinical outcomes, targeting specific 'at risk' population subgroups (e.g. extreme prematurity, long term PN, etc), and exploring the effect of different proportions of lipid constituents are required to evaluate the effectiveness of newer lipid emulsions compared with the conventional pure soy based LE in preterm infants.
Topics: Bronchopulmonary Dysplasia; Emulsions; Fatty Acids, Unsaturated; Fish Oils; Humans; Infant, Newborn; Infant, Premature; Lipids; Olive Oil; Parenteral Nutrition; Plant Oils; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Soybean Oil; Triglycerides; gamma-Linolenic Acid
PubMed: 26630252
DOI: 10.1002/14651858.CD009172.pub2 -
The Cochrane Database of Systematic... Jun 2019Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects in preterm infants. The newer lipid emulsions (LE) from different lipid sources are currently available for use in preterm infants.
OBJECTIVES
To compare the safety and efficacy of all LE for parenteral nutrition (PN) in preterm infants (less than 37 weeks' gestation) including preterm infants with surgical conditions or parenteral nutrition-associated liver disease (PNALD)/cholestasis using direct comparisons and pair-wise meta-analyses.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 July 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and WHO's Trials Registry and Platform), and reference lists of retrieved articles.
SELECTION CRITERIA
Randomised or quasi-randomised controlled studies in preterm infants with or without surgical conditions or PNALD within the first six months of life.
DATA COLLECTION AND ANALYSIS
Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting statistical significance of results.
MAIN RESULTS
We included 29 studies (n = 2037) in this review. LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil-LE (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soybean oil-LE (MFS-LE) and olive-fish-soybean oil-LE (OFS-LE); 2. conventional S-LE; 3. alternative-LE (e.g. MCT-soybean oil-LE (MS-LE), olive-soybean oil-LE and borage oil-based LE).We considered the following broad comparisons: fish oil LE versus non-fish oil LE; fish oil LE versus another fish oil LE; alternative-LE versus S-LE; alternative-LE versus another alternative-LE in preterm infants less than 37 weeks' gestation, preterm infants with surgical conditions and preterm infants with PNALD/cholestasis. Separate subgroup comparisons of each LE preparation were included within these broader groups.Most studies in preterm infants used PN for mean duration of four weeks or less and for longer duration in infants with cholestasis or surgical conditions.We defined the primary outcome of PNALD/cholestasis as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. There was heterogeneity in definitions used by the included studies with Cbil cut-offs ranging from 17.1 μmol/L (1 mg/dL) up to 50 μmol/L (about 3 mg/dL).In preterm infants, meta-analysis found no evidence of a difference in the incidence of PNALD/cholestasis (Cbil cut-off: 2 mg/dl) between fish oil-LEs and all non-fish oil LEs (typical risk ratio (RR) 0.61, 95% confidence interval (CI) 0.24 to 1.56; typical risk difference (RD) -0.03, 95% CI -0.08 to 0.02; 4 studies; n = 328; low-quality evidence).We also considered an outcome allowing for any definition of PNALD (different Cbil cutoffs). In the meta-analysis for PNALD/cholestasis, using any definition and restricted to low or unclear risk of bias studies, there was no evidence of a difference between fish oil LE and all non-fish oil LE for incidence of cholestasis (typical RR 0.80, 95% CI 0.53 to 1.21; typical RD -0.02, 95% CI -0.05 to 0.02; 10 studies; n = 1024; low-quality evidence). There was no evidence of difference in subgroup meta-analyses of individual LE types in any comparison.In preterm infants with surgical conditions or cholestasis, there was only one small study each reporting no evidence of a difference in incidence or resolution of cholestasis respectively with use of a pure F-LE versus S-LE (using a Cbil cut-off of 2 mg/dL).In preterm infants with PNALD/cholestasis (using any definition), the meta-analysis showed significantly less cholestasis with the use of fish oil-LE compared to S-LE (typical RR 0.54, 95% CI 0.32 to 0.91; typical RD -0.39, 95% CI -0.65 to -0.12; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). However, this outcome had a very low number of participants from two small studies with methodological differences, one of which was terminated early, increasing the uncertainty about effect estimates.There were no differences between LE types in pair-wise meta-analyses for growth in preterm infants. There was paucity of studies in preterm infants with surgical conditions or cholestasis to perform meta-analyses for growth and most other outcomes.In the secondary outcomes for preterm infants, there was no difference between fish-oil LE and non-fish oil LE in meta-analysis for severe retinopathy of prematurity (ROP) (stage 3 or greater, or requiring surgery: typical RR 0.80, 95% CI 0.55 to 1.16; typical RD -0.03, 95% CI -0.07 to 0.02; 7 studies; n = 731; very low-quality evidence). There were no differences in the LE types in pair-wise meta-analyses for death, bronchopulmonary dysplasia (BPD), ventilation duration, patent ductus arteriosus, sepsis, necrotising enterocolitis, intraventricular haemorrhage, periventricular leukomalacia, jaundice, hyperglycaemia, hypertriglyceridaemia, intrahepatocellular lipid content and conjugated bilirubin levels in any comparison.In surgical infants, one study (n = 19) reported no differences in death, sepsis rates, Cbil and neurodevelopmental outcomes with pure F-LE versus S-LE.In infants with cholestasis, there were no evidence of differences in death or sepsis in meta-analyses between fish oil-LE and S-LE; (2 studies; n = 40; very low-quality evidence).
AUTHORS' CONCLUSIONS
In the current review, we did not find any particular LE with or without fish oil to be better than another LE in preterm infants for prevention of PNALD/cholestasis, growth, mortality, ROP, BPD and other neonatal outcomes.In preterm infants with surgical conditions or cholestasis, there is currently insufficient evidence from randomised studies to determine with any certainty if fish oil LEs offer advantage in prevention or resolution of cholestasis or in any other clinical outcome.Further research, with larger well-designed trials, is warranted to evaluate the ideal composition of LE in preterm infants and the role of fish oil-containing and other LEs in the prevention and resolution of PNALD, ROP and other clinical outcomes.
Topics: Bilirubin; Bronchopulmonary Dysplasia; Chemical and Drug Induced Liver Injury; Cholestasis; Emulsions; Fish Oils; Humans; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Plant Oils; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Soybean Oil; Surgical Procedures, Operative; gamma-Linolenic Acid
PubMed: 31158919
DOI: 10.1002/14651858.CD013163.pub2