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Research in Developmental Disabilities May 2020Conventional Structural Magnetic Resonance Imaging (sMRI) is a mainstay in Cerebral Palsy (CP) diagnosis.
BACKGROUND
Conventional Structural Magnetic Resonance Imaging (sMRI) is a mainstay in Cerebral Palsy (CP) diagnosis.
AIMS
A systematic literature review was performed with the aim to investigate the relationship between structural brain lesions identified by sMRI and motor outcomes in children with CP.
METHODS
Fifty-eight studies were included. The results were analysed in terms of population characteristics, sMRI (classified according to Krägeloh-Mann & Horber, 2007), gross and fine motor function and their interrelation.
OUTCOMES
White matter lesions were the most common brain lesion types and were present in 57.8 % of all children with uCP, in 67.0 % of all children with bCP and in 33 % of the group of mixed subtypes. Grey matter lesions were most frequently registered in children with dyskinesia (n = 42.2 %). No structural anomalies visualized by sMRI were reported in 5.7 % of all cases. In all lesion types, an equal distribution over the different gross motor function classification system categories was present. The included studies did not report sufficient information about fine motor function to relate these results to structural imaging.
CONCLUSIONS AND IMPLICATIONS
The relationship between brain structure and motor outcome needs to be further elucidated in a representative cohort of children with CP, using a more standardized MRI classification system.
Topics: Adolescent; Brain; Cerebral Palsy; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Dyskinesias; Gait; Gray Matter; Humans; Infant; Leukomalacia, Periventricular; Magnetic Resonance Imaging; Muscle Spasticity; Neuroimaging; White Matter
PubMed: 32192951
DOI: 10.1016/j.ridd.2020.103606 -
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... 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 -
The Cochrane Database of Systematic... Jan 2020Infants 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... (Meta-Analysis)
Meta-Analysis
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 objective To determine the effects of sound reduction on growth and long-term neurodevelopmental outcomes of neonates. Secondary objectives 1. 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), 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, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Noise; Randomized Controlled Trials as Topic; Sound; Stress, Physiological
PubMed: 31986231
DOI: 10.1002/14651858.CD010333.pub3 -
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 -
PloS One 2019Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. (Meta-Analysis)
Meta-Analysis
CONTEXT
Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment.
OBJECTIVE
To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113).
DATA SOURCES
PubMed, Embase, SciELO, LILACS, and Cochrane databases.
STUDY SELECTION
Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period.
DATA EXTRACTION
Two independent researchers extracted data using a predesigned data extraction sheet.
STATISTICAL METHODS
A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation.
RESULTS
Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60-7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57-79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93-14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak.
LIMITATIONS
Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals.
CONCLUSIONS
There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.
Topics: Cerebral Hemorrhage; Hearing Loss; Humans; Infant, Newborn; Infant, Premature; Leukomalacia, Periventricular; Nervous System; Treatment Outcome; Vision Disorders
PubMed: 31600248
DOI: 10.1371/journal.pone.0223427 -
The Cochrane Database of Systematic... Oct 2019Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial... (Review)
Review
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial pressure. PPHN is characterised by failure to adapt to a functional postnatal circulation with a fall in pulmonary vascular resistance. PPHN is responsible for impairment in oxygenation and significant neonatal mortality and morbidity. Prostanoids and their analogues may be useful therapeutic interventions due to their pulmonary vasodilatory and immunomodulatory effects.
OBJECTIVES
Primary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and the need for extracorporeal membrane oxygenation (ECMO) among neonates with PHSecondary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) and improving neurodevelopmental outcomes among neonates with PHComparisons• Prostanoids and their analogues at any dosage or duration used to treat PPHN versus 'standard treatment without these agents', placebo, or inhaled nitric oxide (iNO) therapy• Prostanoids and their analogues at any dosage or duration used to treat refractory PPHN as an 'add-on' therapy to iNO versus iNO alone SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9), MEDLINE via PubMed (1966 to 16 September 2018), Embase (1980 to 16 September 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 September 2018). We also searched clinical trials databases, conference proceedings of the Pediatric Academic Societies (1990 to 16 September 2018), and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We contacted authors who have published in this field as discerned from the reference lists of identified clinical trials and review authors' personal files.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials evaluating prostanoids or their analogues (at any dose, route of administration, or duration) used in neonates at any gestational age less than 28 days' postnatal age for confirmed or suspected PPHN.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal to conduct a systematic review and to assess the methodological quality of included studies (neonatal.cochrane.org/en/index.html). Three review authors independently assessed the titles and abstracts of studies identified by the search strategy and obtained full-text versions for assessment if necessary. We designed forms for trial inclusion or exclusion and for data extraction. We planned to use the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We did not identify any eligible neonatal trials evaluating prostanoids or their analogues as sole agents in the treatment of PPHN.
AUTHORS' CONCLUSIONS
Implications for practiceCurrently, no evidence shows the use of prostanoids or their analogues as pulmonary vasodilators and sole therapeutic agents for the treatment of PPHN in neonates (age 28 days or less).Implications for researchThe safety and efficacy of different preparations and doses and routes of administration of prostacyclins and their analogues in neonates must be established. Well-designed, adequately powered, randomized, multi-center trials are needed to address the efficacy and safety of prostanoids and their analogues in the treatment of PPHN. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes, in addition to short-term outcomes.
PubMed: 31573068
DOI: 10.1002/14651858.CD012963.pub2 -
The Cochrane Database of Systematic... Sep 2019Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard...
BACKGROUND
Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012.
OBJECTIVES
To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36 weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty).
AUTHORS' CONCLUSIONS
Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.
Topics: Blood Transfusion; Cerebral Hemorrhage; Delivery, Obstetric; Female; Humans; Infant, Newborn; Infant, Premature; Placental Circulation; Pregnancy; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Time Factors; Umbilical Cord
PubMed: 31529790
DOI: 10.1002/14651858.CD003248.pub4 -
The Cochrane Database of Systematic... Jul 2019Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may...
BACKGROUND
Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. A drop in inositol levels in infants with respiratory distress syndrome (RDS) can be a sign that their illness will be severe.
OBJECTIVES
To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes including: death (neonatal and infant deaths), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) and sepsis.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 11), MEDLINE via PubMed (1966 to 5 November 2018), Embase (1980 to 5 November 2018), and CINAHL (1982 to 5 November 2018). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials.
SELECTION CRITERIA
We included all randomised controlled trials of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention. Outcomes included neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis.
DATA COLLECTION AND ANALYSIS
The three review authors independently abstracted data on neonatal outcomes and resolved any disagreements through discussion and consensus. Outcomes were reported as typical risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). We used the GRADE approach to assess the quality of evidence.
MAIN RESULTS
Six published randomised controlled trials were identified, with a total of 1177 infants. Study quality varied for the comparison 'Inositol supplementation to preterm infants (repeat doses in any amount and any duration of treatment) versus control' and interim analyses had occurred in several trials for the outcomes of interest. In this comparison, neonatal death was found to be significantly reduced (typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.16 to -0.01; NNTB 11, 95% CI 6 to 100; 3 trials, 355 neonates). Infant deaths were not reduced (typical RR 0.89, 95% CI 0.71 to 1.13; typical RD -0.02, 95% CI -0.07 to 0.02; 5 trials, 1115 infants) (low-quality evidence). ROP stage 2 or higher or stage 3 or higher was not significantly reduced (typical RR 0.89, 95% CI 0.75 to 1.06; typical RD -0.04, 95% CI -0.10 to 0.02; 3 trials, 810 infants) (moderate-quality evidence). There were no significant findings for ROP (any stage), NEC (suspected or proven), sepsis, IVH grade greater than II (moderate-quality evidence). For the comparison 'Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at less than 30 weeks' postmenstrual age (PMA) compared to placebo for preterm infants at risk for or having respiratory distress syndrome' the results from two studies of high quality were included (N = 760 neonates). Recruitment to the larger study (N = 638) was terminated because of a higher rate of deaths in the inositol group. We did not downgrade the quality of the study. The meta-analyses of the outcomes of 'Type 1 ROP or death before determination of ROP outcome using the adjudicated ROP outcome', 'Type 1 ROP including adjudicated ROP outcome', 'All-cause mortality (outcome collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)' and 'Severe IVH (grade 3 or 4)' did not show significant findings (moderate-quality evidence). There were no significant findings for the outcomes 'BPD or death by it prior to 37 weeks' postmenstrual age (outcomes collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)', 'Late onset sepsis (> 72 hours of age)', and 'Suspected or proven NEC' (high-quality evidence).
AUTHORS' CONCLUSIONS
Based on the evidence from randomised controlled trials to date, inositol supplementation does not result in important reductions in the rates of infant deaths, ROP stage 3 or higher, type 1 ROP, IVH grades 3 or 4, BPD, NEC, or sepsis. These conclusions are based mainly on two recent randomised controlled trials in neonates less than 30 weeks' postmenstrual age (N = 760), the most vulnerable population. Currently inositol supplementation should not be routinely instituted as part of the nutritional management of preterm infants with or without RDS. It is important that infants who have been enrolled in the trials included in this review are followed to assess any effects of inositol supplementation on long-term outcomes in childhood. We do not recommend any additional trials in neonates.
Topics: Bronchopulmonary Dysplasia; Dietary Supplements; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Inositol; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Retinopathy of Prematurity; Sepsis; Vitamin B Complex
PubMed: 31283839
DOI: 10.1002/14651858.CD000366.pub4 -
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