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The Cochrane Database of Systematic... Nov 2014Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. BPD is associated with poor long-term respiratory and neurodevelopmental outcome and... (Review)
Review
BACKGROUND
Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. BPD is associated with poor long-term respiratory and neurodevelopmental outcome and increased mortality. The prophylactic use of agents that modulate inflammation such as pentoxifylline, a synthetic methylxanthine and phosphodiesterase inhibitor, may reduce the incidence of BPD.
OBJECTIVES
The primary objective of this review was to determine the effect of pentoxifylline on the incidence of BPD, death prior to 36 weeks postmenstrual age (PMA), and BPD or death prior to 36 weeks PMA in preterm neonates.
SEARCH METHODS
We searched the Cochrane Neonatal Review Group Specialized Register, CENTRAL (The Cochrane Library Issue 9, 2012), EMBASE (January 1974 to September 2012), PubMed (January 1966 to September 2012), and CINAHL (January 1982 to September 2012) in September 2012. We checked references and cross-references from identified studies. We handsearched abstracts from the proceedings of the Pediatric Academic Societies Meetings (from January 1990 to September 2012). We placed no restrictions on language.
SELECTION CRITERIA
Randomised or quasi-randomised clinical trials of systemic or nebulised pentoxifylline in preterm neonates less than 32 weeks gestational age or less than 1500 g birth weight, reporting on at least one outcome of interest, were eligible for inclusion in the review.
DATA COLLECTION AND ANALYSIS
We used the standard methods of the Cochrane Neonatal Review Group and The Cochrane Collaboration. Two review authors (SMS and SK) independently searched the literature as described above and selected studies. Any disagreements were resolved by discussion involving all review authors.
MAIN RESULTS
We identified one randomised clinical trial eligible for inclusion in this review. This study compared the use of nebulised pentoxifylline versus placebo for prevention of BPD in 100 preterm infants and was at high risk of bias due to lack of blinding of intervention and outcome assessors, and incomplete outcome data. There was no statistically significant effect of nebulised pentoxifylline versus placebo on individual outcomes of BPD at 36 weeks PMA or on death prior to 36 weeks PMA. There was no significant effect of nebulised pentoxifylline on intraventricular haemorrhage, periventricular leukomalacia, sepsis, or patent ductus arteriosus (PDA) requiring ligation. The study did not report any of the other secondary outcomes considered for this review. Reporting of adverse events was very limited and did not allow for reliable judgement on the incidence of such events. No long-term outcomes were reported.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine the safety and efficacy of pentoxifylline for prevention of BPD in preterm neonates. We encourage researchers to conduct clinical trials to confirm or refute the role of pentoxifylline for prevention of BPD in preterm neonates. These trials should report on clinically important outcomes and, ideally, on long-term neurodevelopmental outcome.
Topics: Bronchopulmonary Dysplasia; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pentoxifylline; Phosphodiesterase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 25418278
DOI: 10.1002/14651858.CD010018.pub2 -
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 -
Archives of Disease in Childhood. Fetal... Mar 2018Antenatal corticosteroid (ANC) use before 25 weeks' gestation is controversial. Our previous systematic review (eight observational studies, n=10 109) showed that ANC... (Meta-Analysis)
Meta-Analysis Review
Antenatal corticosteroid (ANC) use before 25 weeks' gestation is controversial. Our previous systematic review (eight observational studies, n=10 109) showed that ANC exposure was associated with significantly reduced mortality and severe intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL) in neonates born <25 weeks. We update our review by adding data (n=3334) from a recent study. We used Cochrane methodology and summarised the results using GRADE (The Grading of Recommendations Assessment, Development and Evaluation) guidelines. Nine high-quality observational studies were included. Meta-analysis (random effects model) showed reduced mortality (n=13 443; OR=0.48 (95% CI 0.42 to 0.55) P<0.00001; level of evidence (LOE): moderate) and IVH or PVL (n=8418; OR=0.70 (95% CI 0.63 to 0.79), P<0.00001; LOE: moderate) in neonates born <25 weeks exposed to ANC. There was no difference in necrotising enterocolitis (NEC) ≥stage II (n=8737; OR=1.01 (95% CI 0.84 to 1.22), P=0.89; LOE: low); incidence of chronic lung disease (CLD) was higher (n=7983; OR=1.32 (95% CI 1.04 to 1.67), P=0.02; LOE: low) in ANC group. Composite outcomes of death/major morbidities (eg, severe IVH, NEC, CLD) were improved after ANC exposure.
Topics: Adrenal Cortex Hormones; Cerebral Intraventricular Hemorrhage; Enterocolitis, Necrotizing; Gestational Age; Humans; Infant, Newborn; Leukomalacia, Periventricular; Lung Diseases; Observational Studies as Topic
PubMed: 29208662
DOI: 10.1136/archdischild-2017-313840 -
PloS One 2017Efficacy of antenatal corticosteroids before 25 weeks of gestation is unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Efficacy of antenatal corticosteroids before 25 weeks of gestation is unclear.
OBJECTIVE
To assess and compare neonatal outcomes following ANC exposure at 22, 23 and 24 weeks of gestation by conducting systematic review and meta- analysis.
METHODS
A systematic review of randomised controlled trials (RCT) and non-RCTs reporting on neonatal outcomes after exposure to ANC up to 246 weeks of gestation using the Cochrane systematic review methodology. Databases Pubmed, CINAHL, Embase, Cochrane Central library, and online abstracts of conference proceedings including the Pediatric Academic Society (PAS) were searched in Feb 2017. Primary outcome was in-hospital mortality defined as death before discharge during the first admission. Secondary outcomes included severe intraventricular hemorrhage (IVH> grade III and IV)/or periventricular leukomalacia (PVL), necrotising enterocolitis (NEC >stage II) and chronic lung disease (CLD). Meta-analysis was performed using a random-effects model. The level of evidence (LOE) was summarised using the GRADE guidelines.
MAIN RESULTS
There were no RCTs; 8 high quality non-RCTs were included in the review. Meta-analysis showed reduction in mortality [N = 10109; OR = 0.47(0.39-0.56), p<0.00001; LOE: Moderate] and severe IVH and PVL [N = 5084; OR = 0.71(0.61-0.82), p<0.00001; LOE: Low] after exposure to ANC in neonates born <25 weeks. There was no significant difference in CLD [N = 4649; OR = 1.19(0.85-1.65) p = 0.31; LOE: Low] and NEC [N = 5403; OR = 0.95 (0.76-1.19) p = 0.65; LOE: Low]. Mortality was comparable in neonates born at 22, 23 or 24 weeks.
CONCLUSION
Moderate to low quality evidence indicates that exposure to ANC is associated with reduction in mortality and IVH/or PVL in neonates born before 25 weeks.
Topics: Adrenal Cortex Hormones; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Pregnancy; Pregnancy Outcome
PubMed: 28486556
DOI: 10.1371/journal.pone.0176090 -
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 -
Acta Obstetricia Et Gynecologica... Feb 2019The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent... (Review)
Review
INTRODUCTION
The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent spontaneous preterm birth in women with a prophylactic cerclage.
MATERIAL AND METHODS
Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before June 2018. Keywords included "preterm birth", "prophylactic cerclage", "history-indicated cerclage", "pregnancy" and "17-hydroxyprogesterone caproate". Studies comparing history-indicated cerclage alone with cerclage+17-OHPC were included. The primary outcome measure was preterm birth at <24 weeks of gestation. Secondary outcome measures include preterm birth at <28 weeks, <32 weeks and <37 weeks of gestation, respiratory distress syndrome, necrotizing enterocolitis, fetal birthweight, neonatal intensive care unit stay, mean gestational age at delivery, fetal/neonatal death, neurological morbidity (intraventricular hemorrhage plus periventricular leukomalacia), neonatal sepsis and a composite of severe neonatal morbidity. Severe neonatal morbidity was defined as a composite measure of periventricular leukomalacia, intraventricular hemorrhage (grades III and IV), necrotizing enterocolitis or respiratory distress syndrome. Meta-analysis was performed using the random-effects model of DerSimonian and Laird. Risk of bias and quality assessment were performed using the ROBINS-I and GRADE tools, respectively. PROSPERO Registration Number: CRD42018094559.
RESULTS
Five studies met the inclusion criteria and were included in the final analysis. Of the 546 women, 357 (75%) received history-indicated cerclage alone and 189 (35%) received adjuvant 17-OHPC. The composite endpoint, severe neonatal morbidity, was present in 84 of 1515 neonates. Though there was a trend toward a reduced risk of preterm birth, the summary estimate of effect was not statistically significant when comparing cerclage alone with cerclage+17-OHPC at <24 weeks (relative risk [RR] .86, 95% confidence interval [CI] .45-1.65). Similarly, we found no differences in preterm birth at <37 weeks (RR .90, 95% CI .70-1.17) and <28 weeks (RR .85, 95% CI .54-1.32) when comparing cerclage alone with cerclage+17-OHPC. There were no differences in fetal birthweight, respiratory distress syndrome or necrotizing enterocolitis comparing cerclage alone with cerclage+17-OHPC.
CONCLUSIONS
Intramuscular 17-OHPC in combination with prophylactic cerclage in women with prior preterm birth had no synergistic effect in reducing spontaneous recurrent preterm birth or improving perinatal outcomes.
Topics: 17 alpha-Hydroxyprogesterone Caproate; Cerclage, Cervical; Combined Modality Therapy; Estrogen Antagonists; Female; Humans; Pregnancy; Premature Birth; Secondary Prevention
PubMed: 30339274
DOI: 10.1111/aogs.13488 -
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