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The Cochrane Database of Systematic... Nov 2023Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with... (Review)
Review
BACKGROUND
Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness.
OBJECTIVES
To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.
SEARCH METHODS
We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.
SELECTION CRITERIA
We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO range (MD 13.54%, 95% CI 11.69 to 15.39; I = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS
Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.
Topics: Humans; Infant; Infant, Newborn; Bronchopulmonary Dysplasia; Infant, Premature; Oxygen; Randomized Controlled Trials as Topic; Reproducibility of Results; Retinopathy of Prematurity
PubMed: 38032241
DOI: 10.1002/14651858.CD013294.pub2 -
Ultrasound in Medicine & Biology Jul 2021Cranial ultrasound examinations are routinely performed in very preterm neonates. There is no widespread agreement on the optimal timing of these examinations. This...
Cranial ultrasound examinations are routinely performed in very preterm neonates. There is no widespread agreement on the optimal timing of these examinations. This review examines screening protocols and recommendations available for the timing of cranial ultrasound examinations in preterm neonates born before 32 wk of gestation. A systematic search was performed to find published screening protocols, and 18 articles were included in the final review. The protocols varied in their recommendations on timing, although at least one examination in the first week of life was universally recommended. The recommended timing for a "late" or final ultrasound examination was variable, and included at 6 wks of postnatal age, term-equivalent age or hospital discharge. There was no agreement as to whether weekly or fortnightly sequential ultrasound imaging should be performed after the first week of life. Further studies are required to establish an optimal protocol for these very preterm neonates to improve detection and monitoring of brain injuries.
Topics: Brain Diseases; Clinical Protocols; Echoencephalography; Humans; Infant, Newborn; Infant, Premature; Neonatal Screening
PubMed: 33895036
DOI: 10.1016/j.ultrasmedbio.2021.03.006 -
The Cochrane Database of Systematic... Jan 2017Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used increasingly in neonatal intensive care units (NICUs). However, its effectiveness as a sedative in neonates has not been systematically evaluated.
OBJECTIVES
Primary objeciveTo assess the effectiveness of intravenous midazolam infusion for sedation, as evaluated by behavioural and/or physiological measurements of sedation levels, in critically ill neonates in the NICU. Secondary objectivesTo assess effects of intravenous midazolam infusion for sedation on complications including the following.1. Incidence of intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL).2. Mortality.3. Occurrence of adverse effects associated with the use of midazolam (hypotension, neurological abnormalities).4. Days of ventilation.5. Days of supplemental oxygen.6. Incidence of pneumothorax.7. Length of NICU stay (days).8. Long-term neurodevelopmental outcomes.
SELECTION CRITERIA
We selected for review randomised and quasi-randomised controlled trials of intravenous midazolam infusion for sedation in infants aged 28 days or younger.
DATA COLLECTION AND ANALYSIS
We abstracted data regarding the primary outcome of level of sedation. We assessed secondary outcomes such as intraventricular haemorrhage, periventricular leukomalacia, death, length of NICU stay and adverse effects associated with midazolam. When appropriate, we performed meta-analyses using risk ratios (RRs) and risk differences (RDs), and if the RD was statistically significant, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), along with their 95% confidence intervals (95% CIs) for categorical variables, and weighted mean differences (WMDs) for continuous variables. We assessed heterogeneity by performing the I-squared (I2) test.
MAIN RESULTS
We included in the review three trials enrolling 148 neonates. We identified no new trials for this update. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared with the placebo group. However, none of the sedation scales used have been validated in preterm infants; therefore, we could not ascertain the effectiveness of midazolam in this population. Duration of NICU stay was significantly longer in the midazolam group than in the placebo group (WMD 5.4 days, 95% CI 0.40 to 10.5; I2 = 0%; two studies, 89 infants). One study (43 infants) reported significantly lower Premature Infant Pain Profile (PIPP) scores during midazolam infusion than during dextrose (placebo) infusion (MD -3.80, 95% CI -5.93 to -1.67). Another study (46 infants) observed a higher incidence of adverse neurological events at 28 days' postnatal age (death, grade III or IV IVH or PVL) in the midazolam group compared with the morphine group (RR 7.64, 95% CI 1.02 to 57.21; RD 0.28, 95% CI 0.07 to 0.49; NNTH 4, 95% CI 2 to 14) (tests for heterogeneity not applicable). We considered these trials to be of moderate quality according to GRADE assessment based on the following outcomes: mortality during hospital stay, length of NICU stay, adequacy of analgesia according to PIPP scores and poor neurological outcomes by 28 days' postnatal age.
AUTHORS' CONCLUSIONS
Data are insufficient to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.
Topics: Humans; Hypnotics and Sedatives; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Length of Stay; Midazolam; Randomized Controlled Trials as Topic
PubMed: 28141899
DOI: 10.1002/14651858.CD002052.pub3 -
The Cochrane Database of Systematic... Oct 2017Effective synchronisation of infant respiratory effort with mechanical ventilation may allow adequate gas exchange to occur at lower peak airway pressures, potentially... (Review)
Review
BACKGROUND
Effective synchronisation of infant respiratory effort with mechanical ventilation may allow adequate gas exchange to occur at lower peak airway pressures, potentially reducing barotrauma and volutrauma and development of air leaks and bronchopulmonary dysplasia. During neurally adjusted ventilatory assist ventilation (NAVA), respiratory support is initiated upon detection of an electrical signal from the diaphragm muscle, and pressure is provided in proportion to and synchronous with electrical activity of the diaphragm (EADi). Compared to other modes of triggered ventilation, this may provide advantages in improving synchrony.
OBJECTIVES
Primary• To determine whether NAVA, when used as a primary or rescue mode of ventilation, results in reduced rates of bronchopulmonary dysplasia (BPD) or death among term and preterm newborn infants compared to other forms of triggered ventilation• To assess the safety of NAVA by determining whether it leads to greater risk of intraventricular haemorrhage (IVH), periventricular leukomalacia, or air leaks when compared to other forms of triggered ventilation Secondary• To determine whether benefits of NAVA differ by gestational age (term or preterm)• To determine whether outcomes of cross-over trials performed during the first two weeks of life include peak pressure requirements, episodes of hypocarbia or hypercarbia, oxygenation index, and the work of breathing SEARCH METHODS: We performed searches of the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cohrane Library; MEDLINE via Ovid SP (January 1966 to March 2017); Embase via Ovid SP (January 1980 to March 2017); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host (1982 to March 2017); and the Web of Science (1985 to 2017). We searched abstracts from annual meetings of the Pediatric Academic Societies (PAS) (2000 to 2016); meetings of the European Society of Pediatric Research (published in Pediatric Research); and meetings of the Perinatal Society of Australia and New Zealand (PSANZ) (2005 to 2016). We also searched clinical trials databases to March 2017.
SELECTION CRITERIA
We included randomised and quasi-randomised clinical trials including cross-over trials comparing NAVA with other modes of triggered ventilation (assist control ventilation (ACV),synchronous intermittent mandatory ventilation plus pressure support (SIMV ± PS), pressure support ventilation (PSV), or proportional assist ventilation (PAV)) used in neonates.
DATA COLLECTION AND ANALYSIS
Primary outcomes of interest from randomised controlled trials were all-cause mortality, bronchopulmonary dysplasia (BPD; defined as oxygen requirement at 28 days), and a combined outcome of all-cause mortality or BPD. Secondary outcomes were duration of mechanical ventilation, incidence of air leak, incidence of IVH or periventricular leukomalacia, and survival with an oxygen requirement at 36 weeks' postmenstrual age.Outcomes of interest from cross-over trials were maximum fraction of inspired oxygen, mean peak inspiratory pressure, episodes of hypocarbia, and episodes of hypercarbia measured across the time period of each arm of the cross-over. We planned to assess work of breathing; oxygenation index, and thoraco-abdominal asynchrony at the end of the time period of each arm of the cross-over study.
MAIN RESULTS
We included one randomised controlled study comparing NAVA versus patient-triggered time-cycled pressure-limited ventilation. This study found no significant difference in duration of mechanical ventilation, nor in rates of BPD, pneumothorax, or IVH.
AUTHORS' CONCLUSIONS
Risks and benefits of NAVA compared to other forms of ventilation for neonates are uncertain. Well-designed trials are required to evaluate this new form of triggered ventilation.
Topics: Bronchopulmonary Dysplasia; Cerebral Intraventricular Hemorrhage; Humans; Infant, Newborn; Interactive Ventilatory Support; Leukomalacia, Periventricular; Respiratory Mechanics
PubMed: 29077984
DOI: 10.1002/14651858.CD012251.pub2 -
BMC Pregnancy and Childbirth Nov 2017Given the controversy around mode of delivery, our objective was to assess the evidence regarding the safest mode of delivery for actively resuscitated extremely preterm... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given the controversy around mode of delivery, our objective was to assess the evidence regarding the safest mode of delivery for actively resuscitated extremely preterm cephalic/non-cephalic twin pairs before 28 weeks of gestation.
METHODS
We searched Cochrane CENTRAL, MEDLINE, EMBASE and http://clinicaltrials.gov from January 1994 to January 2017. Two reviewers independently screened titles, abstracts and full text articles, extracted data and assessed risk of bias. We included randomized controlled trials and observational studies. Our primary outcome was a composite of neonatal death (<28 days of life) and severe brain injury in survivors (intraventricular hemorrhage grade ≥ 3 or periventricular leukomalacia). We performed random-effects meta-analyses, generating odds ratios with 95% confidence intervals for the first and second twin separately, and for both twins together. We assessed the risk of bias using a modified Newcastle Ottawa Scale (NOS) for observational studies and used Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).
RESULTS
Our search generated 2695 articles, and after duplicate removal, we screened 2051 titles and abstracts, selecting 113 articles for full-text review. We contacted 36 authors, and ultimately, three observational studies met our inclusion criteria. In cephalic/non-cephalic twin pairs delivered by caesarean section compared to vaginal birth at 24-27 weeks the odds ratio for our composite outcome of neonatal death and severe brain injury for the cephalic first twin was 0.35 (95% CI 0.00-92.61, two studies, I = 76%), 1.69 for the non-cephalic second twin (95% CI 0.04-72.81, two studies, I = 55%) and 0.83 for both twins (95% CI 0.05-13.43, two studies, I = 56%). According to the modified Newcastle Ottawa Scale we assessed individual study quality as being at high risk of bias and according to GRADE the overall evidence for our primary outcomes was very low.
CONCLUSION
Our systematic review on the safest mode of delivery for extremely preterm cephalic/non-cephalic twin pairs found very limited existing evidence, without significant differences in neonatal death and severe brain injury by mode of delivery.
Topics: Adult; Brain Injuries, Traumatic; Breech Presentation; Cesarean Section; Delivery, Obstetric; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Perinatal Death; Pregnancy; Pregnancy, Twin; Twins; Version, Fetal; Young Adult
PubMed: 29187166
DOI: 10.1186/s12884-017-1554-7 -
Frontiers in Neurology 2016Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5-3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from... (Review)
Review
Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5-3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice-Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury.
PubMed: 27199883
DOI: 10.3389/fneur.2016.00057 -
Frontiers in Pediatrics 2022To evaluate the efficacy and safety of oropharyngeal administration of colostrum (OAC) in preterm infants.
OBJECTIVE
To evaluate the efficacy and safety of oropharyngeal administration of colostrum (OAC) in preterm infants.
METHODS
We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the website of the clinical trials, search time was from the establishment of the databases or websites up to 1 February 2022. Preterm infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) ≤ 1500 g were taken as the participants, collect randomized controlled trials (RCTs) of comparing OAC and placebo or no intervention in preterm infants. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature, and we adopted Review Manager 5.3 software for meta-analysis.
RESULTS
In total, 11 RCTs ( = 1,173) were included in the review. A meta-analysis showed significant difference in the incidence of necrotizing enterocolitis [NEC; = 0.009, relative ratio (RR) = 0.51, 95% confidence interval (CI) = 0.31-0.84], late-onset sepsis (LOS; = 0.02, RR = 0.75, 95% CI = 0.59-0.95), ventilator-associated pneumonia (VAP; = 0.03, RR = 0.48, 95% CI = 0.24-0.95), the time to reach full enteral feeds ( < 0.00001, mean difference (MD) = -3.40, 95% CI = -3.87 to -2.92), duration of hospital stay ( < 0.00001, MD = -10.00, 95% CI = -11.36 to -8.64), and the rate of weight gain (kg.d; < 0.00001, MD = 2.63, 95% CI = 2.10-3.16) between the colostrum group and control group. Meanwhile, researchers found no significant difference between the colostrum group and control group in the incidence of bronchopulmonary dysplasia (BPD; = 0.17, RR = 0.83, 95% CI = 0.64-1.08), intraventricular hemorrhage (IVH; grade ≥3; = 0.05, RR = 0.44, 95% CI = 0.19-1.01), periventricular leukomalacia (PVL; = 0.67, RR = 0.70, 95% CI = 0.14-3.49), retinopathy of prematurity (ROP; = 0.29, RR = 1.25, 95% CI = 0.82-1.89), and patent ductus arteriosus (PDA; = 0.17, RR = 1.22, 95% CI = 0.92-1.62).
CONCLUSION
Oropharyngeal administration of colostrum can reduce the incidence of NEC, LOS, and VAP in preterm infants, shortening the time to reach full enteral feeds, and duration of hospital stay, and increasing the rate of weight gain (kg.d). Therefore, OAC can be used as part of routine care for preterm infants.
PubMed: 35832583
DOI: 10.3389/fped.2022.895375 -
The Cochrane Database of Systematic... Jul 2016Preterm prelabour rupture of the membranes (PPROM) complicates approximately 2% of pregnancies and can be either spontaneous or iatrogenic in nature. Complications of... (Review)
Review
BACKGROUND
Preterm prelabour rupture of the membranes (PPROM) complicates approximately 2% of pregnancies and can be either spontaneous or iatrogenic in nature. Complications of PPROM include prematurity, chorioamnionitis, neonatal sepsis, limb position defects, respiratory distress syndrome, pulmonary hypoplasia chronic lung disease, periventricular leukomalacia and intraventricular haemorrhage.A number of different sealing techniques have been employed which aim to restore a physical barrier against infection and encourage the re-accumulation of amniotic fluid. Routine use of sealants is currently not recommended due to a lack of sufficient evidence to support the safety and effectiveness of such interventions.
OBJECTIVES
To assess the effects of sealing techniques following PPROM against each other, or versus standard care (including no sealant), on maternal and neonatal outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing different techniques for sealing preterm prelabour ruptured membranes. Cluster-randomised trials and trials using a cross-over design were not eligible for inclusion in this review. We planned to include abstracts when sufficient information was provided.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy.
MAIN RESULTS
We included two studies (involving 141 women - with data from 124 women). We considered both studies as being at high risk of bias. Meta-analysis was not possible because the included studies examined different interventions (both in comparison with standard care) and reported on few, but different, outcomes. One study compared cervical adapter (mechanical sealing), and the other study examined an immunological membrane sealant. Neither of the included studies reported on this review's primary outcome of interest - perinatal mortality. Similarly, data were not reported for the majority of this review's secondary infant and maternal outcomes. Cervical adapter (mechanical sealing) versus standard care (one study, data from 35 participants)No data were reported for this review's primary outcome - perinatal mortality. Data were reported for few of this review's infant or maternal secondary outcomes.There was no clear difference between the mechanical sealing group and the standard care control in relation to the incidence of neonatal sepsis (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.28 to 5.09 (very low-quality evidence)) or chorioamnionitis (RR 1.19, 95% CI 0.28 to 5.09 (very low-quality evidence)). Oral immunological membrane sealant versus standard care (one study, data from 94 participants)No data were available for perinatal mortality (this review's primary outcome) or for the majority of this review's infant and maternal secondary outcomes. Compared to standard care, the immunological membrane sealant was associated with a reduction in preterm birth less than 37 weeks (RR 0.48, 95% CI 0.34 to 0.68 (very low-quality evidence)) and a reduction in neonatal death (RR 0.38, 95% CI 0.19 to 0.75 (very low-quality evidence)). However, there was no clear difference between groups in terms of neonatal sepsis (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)) or respiratory distress syndrome (RR 0.64, 95% CI 0.28 to 1.46 (very low-quality evidence)).
AUTHORS' CONCLUSIONS
There is insufficient evidence to evaluate sealing procedures for PPROM. There were no data relating to this review's primary outcome (perinatal mortality) and the majority of our infant and maternal secondary outcomes were not reported in the two included studies.There was limited evidence to suggest that an immunological membrane sealant was associated with a reduction in preterm birth at less than 37 weeks and neonatal death, but these results should be interpreted with caution as this is based on one small study, with a high risk of bias, and the intervention has not been tested in other studies.Although midtrimester PPROM is not a rare occurrence, there are only a small amount of published data addressing the benefits and risks of sealing procedures. Most of these studies are retrospective and cohort based and could therefore not be included in our data-analysis.This review highlights the paucity of prospective randomised trials in this area. Current evidence provides limited information both on effectiveness and safety for the interventions described. Given the paucity of high-quality data, we recommend that future research efforts focus on the conduct of randomised trials assessing the effect of promising interventions that have been only evaluated to date in cohort studies (e.g. amniopatch). Future trials should address outcomes including perinatal mortality, preterm birth, neonatal death, respiratory distress syndrome, neonatal sepsis and developmental delay. They should also evaluate maternal outcomes including sepsis, mode of delivery, length of hospital stay and emotional well-being.
Topics: Equipment Design; Female; Fetal Membranes, Premature Rupture; Humans; Immunologic Factors; Negative-Pressure Wound Therapy; Obstetric Labor, Premature; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 27384151
DOI: 10.1002/14651858.CD010218.pub2 -
The Cochrane Database of Systematic... May 2011Clara cell secretary protein (CCSP) is an immune-modulating and anti-inflammatory agent. CCSP is available synthetically as recombinant human Clara cell protein... (Review)
Review
BACKGROUND
Clara cell secretary protein (CCSP) is an immune-modulating and anti-inflammatory agent. CCSP is available synthetically as recombinant human Clara cell protein (rhCC10). It has been shown in animal models to reduce lung injury, improve pulmonary compliance and oxygenation, decrease systemic inflammation and up-regulate surfactant protein and vascular endothelial growth factor expression. These properties makes intratracheally administered CCSP a potential agent in prevention of chronic lung disease (CLD).
OBJECTIVES
To determine the effect of intratracheal CCSP administration compared to placebo or no treatment on morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome (RDS).
SEARCH STRATEGY
We searched CENTRAL (The Cochrane Library, October 2010), MEDLINE and PREMEDLINE (1950 to October 2010), EMBASE (1980 to October 2010) and CINAHL (1982 to October 2010). We searched proceedings of scientific meetings, Google Scholar and reference lists of identified studies, and contacted expert informants and surfactant manufacturers.
SELECTION CRITERIA
Published, unpublished and ongoing randomised controlled, cluster-randomised or quasi-randomised trials of intratracheal CCSP administration, compared to placebo or no treatment on morbidity and mortality in preterm infants at risk of RDS.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for eligibility and quality, and extracted data.
MAIN RESULTS
One pilot study was identified and included. This study enrolled 22 preterm infants 700 to 1300g with established RDS who required ventilation for surfactant administration. Infants received one intratracheal dose of placebo (n = 7), 1.5 mg/kg (n = 8) or 5 mg/kg (n = 7) rhCC10 within four hours of surfactant treatment. At either dose of rhCC10, no significant difference was reported in CLD (36 weeks postmenstrual age or 28 days), mortality, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, sepsis or days supplemental oxygen compared to placebo. A significant increase in days mechanical ventilation was reported for infants receiving rhCC10 5mg/kg (mean difference 12.00, 95% confidence interval 0.39 to 23.61) but not at the lower dose. The study reported that a single intratracheal dose of rhCC10 was well tolerated and resulted in a significant reduction in tracheal aspirate neutrophil and total cell count, and lung protein concentration. There was no significant difference reported in tracheal aspirate cytokine levels between groups.
AUTHORS' CONCLUSIONS
There are insufficient data to determine the role of rhCC10 in clinical practice. Further studies are required to determine if rhCC10 reduces lung inflammation in infants at risk of CLD, and to determine dose and dosing strategy.
Topics: Anti-Inflammatory Agents; Humans; Infant, Newborn; Infant, Premature; Pilot Projects; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Distress Syndrome, Newborn; Trachea; Uteroglobin
PubMed: 21563168
DOI: 10.1002/14651858.CD008308.pub2 -
The Cochrane Database of Systematic... Oct 2006L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity, and acidifies the solution, thereby increasing calcium and phosphate solubility, and potentially improving bone mineralization.
OBJECTIVES
To determine the effects of supplementing parenteral nutrition with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes.
SEARCH STRATEGY
The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE (1966-December 2005), EMBASE (1974-December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and recent abstracts (until December 2005) from the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were searched.
SELECTION CRITERIA
All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed. Predetermined outcome variables included growth, nitrogen retention, mortality, morbidity secondary to oxidation injury, bone accretion, acidosis, liver disease, and cysteine levels.
DATA COLLECTION AND ANALYSIS
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD).
MAIN RESULTS
Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (< or = 1000 grams).
PRIMARY OUTCOMES
Growth was not significantly affected by cysteine supplementation (evaluated in one quasi-randomized trial) or by N-acetylcysteine supplementation (evaluated in one RCT). Nitrogen retention was significantly increased by cysteine supplementation (studied in four trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants).
SECONDARY OUTCOMES
Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH. No data were available on other outcomes.
AUTHORS' CONCLUSIONS
Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance.However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants. A large RCT would be required to assess whether routine prolonged cysteine supplementation of cysteine-free PN affects growth and short and long-term neonatal outcomes in very low birth weight infants.
Topics: Acetylcysteine; Cysteine; Cystine; Dietary Supplements; Humans; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Randomized Controlled Trials as Topic
PubMed: 17054219
DOI: 10.1002/14651858.CD004869.pub2