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American Journal of Obstetrics &... Nov 2020This study aimed to estimate the effect of antenatal corticosteroid administration on neonatal mortality and morbidity in preterm small-for-gestational age infants... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to estimate the effect of antenatal corticosteroid administration on neonatal mortality and morbidity in preterm small-for-gestational age infants through a systematic review and meta-analysis.
DATA SOURCES
A predefined, systematic search was conducted through Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trial Registry Platform, and ClinicalTrials.gov yielding 5324 articles from 1970 to 2019.
STUDY ELIGIBILITY CRITERIA
Eligible studies compared neonatal morbidity and mortality among small-for-gestational age infants delivered preterm who received antenatal corticosteroids with those who did not.
METHODS
The primary outcome was neonatal mortality. Secondary outcomes were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia, bronchopulmonary dysplasia or chronic lung disease of prematurity, or neonatal sepsis. We assessed heterogeneity by means of Higgins I statistic and Cochran's Q test and calculated pooled odds ratios with 95% confidence intervals using random effects models.
RESULTS
A total of 16 observational cohort and case-control studies published from 1995 to 2018 met the selection criteria for the systematic review and included 8989 preterm small-for-gestational age infants. Antenatal corticosteroid administration was explicitly reported among 8376 small-for-gestational age infants; 4631 (55.3%) received antenatal corticosteroids and 3741 (44.7%) did not. Of note, 13 studies including 6387 preterm small-for-gestational age infants were then included in the meta-analysis. Neonatal mortality was significantly lower among infants who received antenatal corticosteroids than those who did not (12 studies: 12.8% vs 15.1%; pooled odds ratio, 0.63; 95% confidence interval, 0.46-0.86), with significant heterogeneity between studies (I=55.1%; P=.011). There was no significant difference in respiratory distress syndrome (12 studies: odds ratio, 0.89; 95% confidence interval, 0.69-1.15), necrotizing enterocolitis (7 studies: odds ratio, 0.93; 95% confidence interval, 0.70-1.22), intraventricular hemorrhage and periventricular leukomalacia (10 studies: odds ratio, 0.82; 95% confidence interval, 0.56-1.20), bronchopulmonary dysplasia or chronic lung disease of prematurity (8 studies: odds ratio, 1.11; 95% confidence interval, 0.88-1.41), or neonatal sepsis (6 studies: odds ratio, 1.13; 95% confidence interval, 0.86-1.49).
CONCLUSION
These data indicate that antenatal corticosteroid administration reduces neonatal mortality in small-for-gestational age infants delivered preterm, with no apparent effect on neonatal morbidity. This supports the use of antenatal corticosteroids to reduce neonatal mortality in pregnancies with small-for-gestational age infants at risk of preterm birth.
Topics: Adrenal Cortex Hormones; Bronchopulmonary Dysplasia; Female; Gestational Age; Humans; Infant; Infant, Newborn; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn
PubMed: 33345924
DOI: 10.1016/j.ajogmf.2020.100215 -
Expert Opinion on Investigational Drugs Mar 2022Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral...
INTRODUCTION
Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral palsy in preterm neonates. There is no proven therapy for PVL. This calls for appraisal of targeted therapies that have been investigated in animal models to evaluate their relevance in a clinical research context.
AREAS COVERED
This systematic review identifies interventions that were evaluated in preclinical studies for neuroprotective efficacy against PVL. We identified 142 studies evaluating various interventions in PVL animal models (search method is detailed in section 2).
EXPERT OPINION
Interventions that have yielded significant results in preclinical research, and that have been evaluated in a limited number of clinical trials include stem cells, erythropoietin, and melatonin. Many other therapeutic modalities evaluated in preclinical studies have been identified, but more data on their neuroprotective potential in PVL must be garnered before they can be considered for clinical trials. Because most of the tested interventions had only a partial efficacy, a combination of interventions that could be synergistic should be investigated in future preclinical studies. Furthermore, since the nature and pattern of perinatal insults to preterm brain predisposing it to PVL are substantially variable, individualized approaches for the choice of appropriate neuroprotective interventions tailored to different subgroups of preterm neonates should be explored.
Topics: Animals; Brain; Female; Humans; Infant, Newborn; Leukomalacia, Periventricular; Pregnancy; Risk Factors
PubMed: 35143732
DOI: 10.1080/13543784.2022.2040479 -
Resuscitation Feb 2023Initial management of inadequate adaptation to extrauterine life relies on non-invasive respiratory support. Two types of devices are available: fixed pressure devices... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Initial management of inadequate adaptation to extrauterine life relies on non-invasive respiratory support. Two types of devices are available: fixed pressure devices (FPD; T-pieces or ventilators) and hand driven pressure devices (HDPD; self- or flow-inflating bags). This systematic review and meta-analysis aims to compare clinical outcomes after neonatal resuscitation according to device type.
METHODS
Four databases were searched from inception to 2022, January. Search strategies included Mesh/Emtree terms as well as free language without any restriction. Randomized, quasi-randomized studies and prospective cohorts comparing the use of the two types of devices in neonatal resuscitation were included.
RESULTS
Nine studies recruiting 3621 newborns were included: 5 RCTs, 2 RCTs with interventions bundles and 2 prospective cohorts. Meta-analysis of the 5 RCTs demonstrated significant reductions in bronchopulmonary dysplasia (RR0,68[0,48-0,96]-NNT 31) and other respiratory outcomes: intubation in the delivery room (RR0,72[0,58-0,88]-NNT 13,4), mechanical ventilation requirements (RR0,81[0,67-0,96]-NNT 17) and duration (MD-1,54 days[-3,03- -0,05]), need for surfactant (RR0,79[0,64-0,96]-NNT 7,3). The overall analysis found a lower mortality in the FPD group (OR0,57[0,47-0,69]-NNT 12,7) and confirmed decreases in intubation, surfactant requirement and mechanical ventilation rates (OR 0,56[0,40-0,79]- NNT7,5; OR 0,67[0,55-0,82]-NNT10,7 and OR0,58[0,42-0,80]- NNT 7,4 respectively). The risk of cystic periventricular leukomalacia (cPVL) decreased significantly with FPD (OR0.59[0.41-0.85]-NNT 27). Pneumothorax rates were similar (OR0.82[0.44-1.52]).
CONCLUSION AND RELEVANCE
Resuscitation at birth with FPD improves respiratory transition and decreases BPD with a very low to moderate certainty of evidence. There is suggestion of decreases in mortality and cPVL. Further studies are still needed to confirm those results.
Topics: Infant, Newborn; Humans; Resuscitation; Infant, Premature; Prospective Studies; Respiration, Artificial; Pulmonary Surfactants; Surface-Active Agents
PubMed: 36623747
DOI: 10.1016/j.resuscitation.2022.109681 -
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 -
Antioxidants (Basel, Switzerland) Sep 2021A widely accepted concept is that boys are more susceptible than girls to oxidative stress-related complications of prematurity, including bronchopulmonary dysplasia... (Review)
Review
A widely accepted concept is that boys are more susceptible than girls to oxidative stress-related complications of prematurity, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL). We aimed to quantify the effect size of this male disadvantage by performing a systematic review and meta-analysis of cohort studies exploring the association between sex and complications of prematurity. Risk ratios (RRs) and 95% CIs were calculated by a random-effects model. Of 1365 potentially relevant studies, 41 met the inclusion criteria (625,680 infants). Male sex was associated with decreased risk of hypertensive disorders of pregnancy, fetal distress, and C-section, but increased risk of low Apgar score, intubation at birth, respiratory distress, surfactant use, pneumothorax, postnatal steroids, late onset sepsis, any NEC, NEC > stage 1 (RR 1.12, CI 1.06-1.18), any IVH, severe IVH (RR 1.28, CI 1.22-1.34), severe IVH or PVL, any BPD, moderate/severe BPD (RR 1.23, CI 1.18-1.27), severe ROP (RR 1.14, CI 1.07-1.22), and mortality (RR 1.23, CI 1.16-1.30). In conclusion, preterm boys have higher clinical instability and greater need for invasive interventions than preterm girls. This leads to a male disadvantage in mortality and short-term complications of prematurity.
PubMed: 34573122
DOI: 10.3390/antiox10091490 -
Pediatric Neurology Nov 2021We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.
METHODS
Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
RESULTS
One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL.
CONCLUSION
Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Leukomalacia, Periventricular; Risk Factors
PubMed: 34537463
DOI: 10.1016/j.pediatrneurol.2021.08.003 -
Frontiers in Pediatrics 2022Vitamin A plays an important role in the development and maintenance of the normal function of organs and systems. Premature infants have low levels of vitamin A, which...
BACKGROUND
Vitamin A plays an important role in the development and maintenance of the normal function of organs and systems. Premature infants have low levels of vitamin A, which may be associated with an increased risk of developing disease. This study aimed to evaluate the effects of vitamin A supplementation on short-term morbidity and mortality in very-low-birth-weight (VLBW) infants.
METHODS
We used PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science to conduct a literature search of studies published before January 1, 2022, to be included in our meta-analysis. The analysis included randomized controlled trials that compared the effects of vitamin A supplementation on VLBW infants (birth weight <1,500 g) and controls given a placebo or no treatment. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines.
RESULTS
Twelve randomized controlled trials were included in the meta-analysis, and 2,111 infants were pooled and analyzed. The overall risk of bias was not serious in the included studies. Vitamin A supplementation for reducing the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age seems to be limited [risk ratio (RR):0.85; 95% confidence intervals (CI): 0.70-1.04; 8 studies, 1,595 infants, very-low-certainty evidence], which is different from the previous systematic review. Length of hospital stay (mean difference: -12.67, 95% CI: -23.55 to -1.79; 6 studies, 739 infants, low-certainty evidence), and the incidence of vitamin A deficiency at 28 days postnatal age (RR: 0.08; 95% CI: 0.02-0.38; 3 studies, 358 infants, low-certainty evidence) were reduced in the vitamin A group. Besides, vitamin A supplementation seems to reduce the incidence of periventricular leukomalacia (RR: 0.68; 95% CI: 0.47-0.97; 4 studies, 1,224 infants, low-certainty evidence) and retinopathy of prematurity of any grade (RR: 0.61; 95% CI: 0.48-0.76; 4 studies, 463 infants, moderate-certainty evidence).
CONCLUSIONS
There is no sufficient evidence regarding vitamin A supplementation preventing BPD in VLBW infants. Vitamin A supplementation can reduce the incidence of vitamin A deficiency and retinopathy of prematurity of any grade, and may exert an effect of preventing periventricular leukomalacia.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020211070.
PubMed: 35463913
DOI: 10.3389/fped.2022.788409 -
The Cochrane Database of Systematic... Jun 2023Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.
OBJECTIVES
To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We also searched the reference lists of identified clinical trials and handsearched conference abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs assessing the efficacy of PTX with antibiotics (any dose or duration) for treatment of suspected or confirmed sepsis or NEC in neonates. We included three comparisons: (1) PTX with antibiotics compared to placebo or no intervention with antibiotics; (2) PTX with antibiotics compared to PTX with antibiotics and adjunct treatments such as immunoglobulin M-enriched intravenous immunoglobulin (IgM-enriched IVIG); (3) PTX with antibiotics compared to adjunct treatments such as IgM-enriched IVIG with antibiotics.
DATA COLLECTION AND ANALYSIS
We reported typical risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes derived from a fixed-effect model of meta-analysis. We calculated the number needed to treat for an additional beneficial outcome (NNTB) if there was a statistically significant reduction in RD.
MAIN RESULTS
We identified no new studies for this update. We included six RCTs (416 neonates). All of the included studies examined neonates with sepsis; we identified no studies on neonates with NEC. Four of the six trials had high risk of bias for at least one risk of bias domain. Comparison 1: PTX with antibiotics compared to placebo with antibiotics, or antibiotics alone, in neonates with sepsis may reduce all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-certainty evidence) and may decrease length of hospital stay (LOS) (MD -7.74, 95% CI -11.72 to -3.76; 2 studies, 157 participants, low-certainty evidence). The evidence is very uncertain that PTX with antibiotics compared to placebo or no intervention results in any change in chronic lung disease (CLD) (RR 1.50, 95% CI 0.45 to 5.05; 1 study, 120 participants, very low-certainty evidence), severe intraventricular haemorrhage (sIVH) (RR 0.75, 95% CI 0.28 to 2.03; 1 study, 120 participants, very low-certainty evidence), periventricular leukomalacia (PVL) (RR 0.50, 95% CI 0.10 to 2.63; 1 study, 120 participants, very low-certainty evidence), NEC (RR 0.56, 95% CI 0.29 to 1.06; 6 studies, 405 participants, very low-certainty evidence), or retinopathy of prematurity (ROP) (RR 0.40, 95% CI 0.08 to 1.98; 1 study, 120 participants, very low-certainty evidence) in neonates with sepsis. Comparison 2: the evidence is very uncertain that PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG has any effect on mortality (RR 0.71, 95% CI 0.24 to 2.10; 102 participants, 1 study, very low-certainty evidence) or development of NEC in neonates with sepsis (RR 1.33, 95% CI 0.31 to 5.66; 1 study, 102 participants, very low-certainty evidence). The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. Comparison 3: the evidence is very uncertain that PTX with antibiotics compared to IgM-enriched IVIG with antibiotics has any effect on mortality (RR 1.25, 95% CI 0.36 to 4.39; 102 participants, 1 study, very low-certainty evidence) or development of NEC (RR 1.33, 95% CI 0.31 to 5.66; 102 participants, 1 study, very low-certainty evidence) in neonates with sepsis. The outcomes of CLD, sIVH, PVL, LOS, and ROP were not reported. All of the included studies evaluated adverse effects due to PTX, but none were reported in the intervention group in any of the comparisons.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that adjunct PTX therapy in neonatal sepsis may decrease mortality and length of hospital stay without any adverse effects. The evidence is very uncertain if PTX with antibiotics compared to PTX with antibiotics and IgM-enriched IVIG, or PTX with antibiotics compared to IgM-enriched IVIG with antibiotics, has any effect on mortality or development of NEC. We encourage researchers to undertake well-designed multicentre trials to confirm or refute the effectiveness and safety of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Enterocolitis, Necrotizing; Immunoglobulin M; Immunoglobulins, Intravenous; Infant, Premature; Lung Diseases; Neonatal Sepsis; Pentoxifylline; Retinopathy of Prematurity; Sepsis
PubMed: 37338074
DOI: 10.1002/14651858.CD004205.pub4 -
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 -
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