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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 -
Ultrasound in Obstetrics & Gynecology :... Jan 2019To explore the impact of severity and management (expectant, laser treatment or selective reduction) on perinatal outcome of monochorionic twin pregnancies complicated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the impact of severity and management (expectant, laser treatment or selective reduction) on perinatal outcome of monochorionic twin pregnancies complicated by selective fetal growth restriction (sFGR).
METHODS
MEDLINE, EMBASE, CINAHL, ClinicalTrials.gov and The Cochrane Library databases were searched for studies on outcome following expectant management, laser treatment or selective reduction in monochorionic twin pregnancies complicated by sFGR. Only pregnancies affected by sFGR and categorized according to the Gratacós classification (Type I, II or III) were included. The primary outcome was mortality, including single and double intrauterine (IUD), neonatal (NND) and perinatal deaths. Secondary outcomes were neonatal morbidity, abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, respiratory distress syndrome, admission to neonatal intensive care unit and survival free from neurological complications (intact survival). Meta-analyses of proportions were used to analyze the extracted data according to management, severity of sFGR and fetal size (smaller vs larger twin).
RESULTS
Sixteen observational studies (786 monochorionic twin pregnancies) were included. In pregnancies complicated by Type-I sFGR managed expectantly, IUD occurred in 3.1% (95% CI, 1.1-5.9%) of fetuses and 97.9% (95% CI, 93.6-99.9%) of twins had intact survival. In pregnancies complicated by Type-I sFGR treated using laser therapy, IUD occurred in 16.7% (95% CI, 0.4-64.1%) of fetuses and, in those treated using selective reduction, IUD occurred in 0% (95% CI, 0-34.9%) of cotwins, with no evidence of neurological complications in the survivors. In pregnancies complicated by Type-II sFGR managed expectantly, IUD occurred in 16.6% (95% CI, 6.9-29.5%) and NND in 6.4% (95% CI, 0.2-28.2%) of fetuses, and 89.3% (95% CI, 71.8-97.7%) of twins survived without neurological compromise. In Type-II sFGR pregnancies treated using laser therapy, IUD occurred in 44.3% (95% CI, 22.2-67.7%) of fetuses, while none of the affected cases experienced morbidity and survivors were free of neurological complications. Of pregnancies undergoing selective reduction, IUD of the cotwin occurred in 5.0% (95% CI, 0.03-20.5%) and NND in 3.7% (95% CI, 0.2-11.1%), and 90.6% (95% CI, 42.3-94.3%) of surviving cotwins were free from neurological complications. In pregnancies complicated by Type-III sFGR managed expectantly, IUD occurred in 13.2% (95% CI, 7.2-20.5%) and NND in 6.8% (95% CI, 0.7-18.6%) of fetuses, and 61.9% (95% CI, 38.4-81.9%) of twins had intact survival. In pregnancies complicated by Type-III sFGR treated with laser therapy, IUD occurred in 32.9% (95% CI, 20.9-46.2%) of fetuses and all surviving twins were without neurological complications. Finally, in pregnancies with Type-III sFGR treated with selective reduction, NND occurred in 5.2% (95% CI, 0.8-12.8%) of cotwins and 98.8% (95% CI, 93.9-99.9%) had intact survival.
CONCLUSION
Type-I sFGR is characterized by good perinatal outcome when managed expectantly, which represents the most reasonable management strategy for the large majority of affected cases. Pregnancies complicated by Type-II or -III sFGR treated with fetoscopic laser ablation have a higher rate of mortality but lower rate of morbidity compared with those managed expectantly, supporting the use of fetal therapy at gestations remote from neonatal viability. Data on outcome following selective reduction are scarce. In view of the lack of evidence from randomized controlled trials, prenatal management of sFGR should be individualized according to gestational age at diagnosis, severity of growth discordance and magnitude of Doppler anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Female; Fetal Growth Retardation; Humans; Infant, Newborn; Perinatal Mortality; Pregnancy; Pregnancy Outcome; Pregnancy, Twin; Twins, Monozygotic
PubMed: 30207011
DOI: 10.1002/uog.20114 -
The Cochrane Database of Systematic... May 2018Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO - proportion of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO - proportion of the breathed air that is oxygen) targeted to oxygen saturation (SpO - an estimate of the amount of oxygen in the blood) for infants born preterm is unclear.
OBJECTIVES
To determine whether lower or higher initial oxygen concentrations, when titrated according to oxygen saturation targets during the resuscitation of preterm infants at birth, lead to improved short- and long-term mortality and morbidity.
SEARCH METHODS
We conducted electronic searches of the Cochrane Central Register of Controlled Trials (13 October 2017), Ovid MEDLINE (1946 to 13 October 2017), Embase (1974 to 13 October 2017) and CINAHL (1982 to 13 October 2017); we also searched previous reviews (including cross-references), contacted expert informants, and handsearched journals.
SELECTION CRITERIA
We included randomised controlled trials (including cluster- and quasi-randomised trials) which enrolled preterm infants requiring resuscitation following birth and allocated them to receive either lower (FiO < 0.4) or higher (FiO ≥ 0.4) initial oxygen concentrations titrated to target oxygen saturation.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. Primary outcomes included mortality near term or at discharge (latest reported) and neurodevelopmental disability. We conducted meta-analysis using a fixed-effect model. We assessed the quality of the evidence using GRADE.
MAIN RESULTS
The search identified 10 eligible trials. Meta-analysis of the 10 included studies (914 infants) showed no difference in mortality to discharge between lower (FiO < 0.4) and higher (FiO ≥ 0.4) initial oxygen concentrations targeted to oxygen saturation (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.68 to 1.63). We identified no heterogeneity in this analysis. We graded the quality of the evidence as low due to risk of bias and imprecision. There were no significant subgroup effects according to inspired oxygen concentration strata (FiO 0.21 versus ≥ 0.4 to < 0.6; FiO 0.21 versus ≥ 0.6 to 1.0; and FiO ≥ 0.3 to < 0.4 versus ≥ 0.6 to 1.0). Subgroup analysis identified a single trial that reported increased mortality from use of lower (FiO 0.21) versus higher (FiO 1.0) initial oxygen concentration targeted to a lowest SpO of less than 85%, whereas meta-analysis of nine trials targeting a lowest SpO of 85% to 90% found no difference in mortality.Meta-analysis of two trials (208 infants) showed no difference in neurodevelopmental disability at 24 months between infants receiving lower (FiO < 0.4) versus higher (FiO > 0.4) initial oxygen concentrations targeted to oxygen saturation. Other outcomes were incompletely reported by studies. Overall, we found no difference in use of intermittent positive pressure ventilation or intubation in the delivery room; retinopathy (damage to the retina of the eyes, measured as any retinopathy and severe retinopathy); intraventricular haemorrhage (any and severe); periventricular leukomalacia (a type of white-matter brain injury); necrotising enterocolitis (a condition where a portion of the bowel dies); chronic lung disease at 36 weeks' gestation; mortality to follow up; postnatal growth failure; and patent ductus arteriosus. We graded the quality of the evidence for these outcomes as low or very low.
AUTHORS' CONCLUSIONS
There is uncertainty as to whether initiating post birth resuscitation in preterm infants using lower (FiO < 0.4) or higher (FiO ≥ 0.4) oxygen concentrations, targeted to oxygen saturations in the first 10 minutes, has an important effect on mortality or major morbidity, intubation during post birth resuscitation, other resuscitation outcomes, and long-term outcomes including neurodevelopmental disability. We assessed the quality of the evidence for all outcomes as low to very low. Further large, well designed trials are needed to assess the effect of using different initial oxygen concentrations and the effect of targeting different oxygen saturations.
Topics: Cerebral Hemorrhage; Child, Preschool; Enterocolitis, Necrotizing; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Lung Diseases; Neurodevelopmental Disorders; Oxygen; Randomized Controlled Trials as Topic; Resuscitation; Retinopathy of Prematurity
PubMed: 29726010
DOI: 10.1002/14651858.CD010239.pub2 -
The Cochrane Database of Systematic... Mar 2018Sick newborn and preterm infants frequently are not able to be fed enterally, necessitating parenteral fluid and nutrition. Potential benefits of higher parenteral amino... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sick newborn and preterm infants frequently are not able to be fed enterally, necessitating parenteral fluid and nutrition. Potential benefits of higher parenteral amino acid (AA) intake for improved nitrogen balance, growth, and infant health may be outweighed by the infant's ability to utilise high intake of parenteral AA, especially in the days after birth.
OBJECTIVES
The primary objective is to determine whether higher versus lower intake of parenteral AA is associated with improved growth and disability-free survival in newborn infants receiving parenteral nutrition.Secondary objectives include determining whether:• higher versus lower starting or initial intake of amino acids is associated with improved growth and disability-free survival without side effects;• higher versus lower intake of amino acids at maximal intake is associated with improved growth and disability-free survival without side effects; and• increased amino acid intake should replace non-protein energy intake (glucose and lipid), should be added to non-protein energy intake, or should be provided simultaneously with non-protein energy intake.We conducted subgroup analyses to look for any differences in the effects of higher versus lower intake of amino acids according to gestational age, birth weight, age at commencement, and condition of the infant, or concomitant increases in fluid intake.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (2 June 2017), MEDLINE (1966 to 2 June 2017), Embase (1980 to 2 June 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 2 June 2017). We also searched clinical trials databases, conference proceedings, and citations of articles.
SELECTION CRITERIA
Randomised controlled trials of higher versus lower intake of AAs as parenteral nutrition in newborn infants. Comparisons of higher intake at commencement, at maximal intake, and at both commencement and maximal intake were performed.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed trial quality, and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs) and assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
Thirty-two studies were eligible for inclusion. Six were short-term biochemical tolerance studies, one was in infants at > 35 weeks' gestation, one in term surgical newborns, and three yielding no usable data. The 21 remaining studies reported clinical outcomes in very preterm or low birth weight infants for inclusion in meta-analysis for this review.Higher AA intake had no effect on mortality before hospital discharge (typical RR 0.90, 95% CI 0.69 to 1.17; participants = 1407; studies = 14; I = 0%; quality of evidence: low). Evidence was insufficient to show an effect on neurodevelopment and suggest no reported benefit (quality of evidence: very low). Higher AA intake was associated with a reduction in postnatal growth failure (< 10th centile) at discharge (typical RR 0.74, 95% CI 0.56 to 0.97; participants = 203; studies = 3; I = 22%; typical RD -0.15, 95% CI -0.27 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 4 to 50; quality of evidence: very low). Subgroup analyses found reduced postnatal growth failure in infants that commenced on high amino acid intake (> 2 to ≤ 3 g/kg/day); that occurred with increased amino acid and non-protein caloric intake; that commenced on intake at < 24 hours' age; and that occurred with early lipid infusion.Higher AA intake was associated with a reduction in days needed to regain birth weight (MD -1.14, 95% CI -1.73 to -0.56; participants = 950; studies = 13; I = 77%). Data show varying effects on growth parameters and no consistent effects on anthropometric z-scores at any time point, as well as increased growth in head circumference at discharge (MD 0.09 cm/week, 95% CI 0.06 to 0.13; participants = 315; studies = 4; I = 90%; quality of evidence: very low).Higher AA intake was not associated with effects on days to full enteral feeds, late-onset sepsis, necrotising enterocolitis, chronic lung disease, any or severe intraventricular haemorrhage, or periventricular leukomalacia. Data show a reduction in retinopathy of prematurity (typical RR 0.44, 95% CI 0.21 to 0.93; participants = 269; studies = 4; I = 31%; quality of evidence: very low) but no difference in severe retinopathy of prematurity.Higher AA intake was associated with an increase in positive protein balance and nitrogen balance. Potential biochemical intolerances were reported, including risk of abnormal blood urea nitrogen (typical RR 2.77, 95% CI 2.13 to 3.61; participants = 688; studies = 7; I = 6%; typical RD 0.26, 95% CI 0.20 to 0.32; number needed to treat for an additional harmful outcome (NNTH) 4; 95% CI 3 to 5; quality of evidence: high). Higher amino acid intake in parenteral nutrition was associated with a reduction in hyperglycaemia (> 8.3 mmol/L) (typical RR 0.69, 95% CI 0.49 to 0.96; participants = 505; studies = 5; I = 68%), although the incidence of hyperglycaemia treated with insulin was not different.
AUTHORS' CONCLUSIONS
Low-quality evidence suggests that higher AA intake in parenteral nutrition does not affect mortality. Very low-quality evidence suggests that higher AA intake reduces the incidence of postnatal growth failure. Evidence was insufficient to show an effect on neurodevelopment. Very low-quality evidence suggests that higher AA intake reduces retinopathy of prematurity but not severe retinopathy of prematurity. Higher AA intake was associated with potentially adverse biochemical effects resulting from excess amino acid load, including azotaemia. Adequately powered trials in very preterm infants are required to determine the optimal intake of AA and effects of caloric balance in parenteral nutrition on the brain and on neurodevelopment.
Topics: Amino Acids; Child Development; Developmental Disabilities; Humans; Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Randomized Controlled Trials as Topic; Retinopathy of Prematurity
PubMed: 29505664
DOI: 10.1002/14651858.CD005949.pub2 -
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 -
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 -
The Cochrane Database of Systematic... Nov 2017Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia and to provide neuro protection and protection against necrotising enterocolitis (NEC). Darbepoetin (Darbe) and EPO are currently available ESAs.
OBJECTIVES
To assess the effectiveness and safety of ESAs (erythropoietin (EPO) and/or Darbe) initiated early (before eight days after birth) compared with placebo or no intervention in reducing red blood cell (RBC) transfusions, adverse neurological outcomes, and feeding intolerance including necrotising enterocolitis (NEC) in preterm and/or low birth weight infants. Primary objective for studies that primarily investigate the effectiveness and safety of ESAs administered early in reducing red blood cell transfusions:To assess the effectiveness and safety of ESAs initiated early in reducing red blood cell transfusions in preterm infants. Secondary objectives:Review authors performed subgroup analyses of low (≤ 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and the amount of iron supplementation provided: none, low (≤ 5 mg/kg/d), and high (> 5 mg/kg/d). Primary objective for studies that primarily investigate the neuro protective effectiveness of ESAs:To assess the effectiveness and safety of ESAs initiated early in reducing adverse neurological outcomes in preterm infants. Primary objective for studies that primarily investigate the effectiveness of EPO or Darbe administered early in reducing feeding intolerance:To assess the effectiveness and safety of ESAs administered early in reducing feeding intolerance (and NEC) in preterm infants. Other secondary objectives:To compare the effectiveness of ESAs in reducing the incidence of adverse events and improving long-term neurodevelopmental outcomes.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE via PubMed (1966 to 10 March 2017), Embase (1980 to 10 March 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 10 March 2017). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised and quasi-randomised controlled trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of early initiation of EAS treatment versus placebo or no intervention in preterm or low birth weight infants.
DATA COLLECTION AND ANALYSIS
We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and the GRADE approach to assess the quality of evidence.
MAIN RESULTS
This updated review includes 34 studies enrolling 3643 infants. All analyses compared ESAs versus a control consisting of placebo or no treatment.Early ESAs reduced the risk of 'use of one or more [red blood cell] RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.74 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I = 69% for RR and 62% for RD (moderate heterogeneity); number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 6 to 10; 19 studies, 1750 infants). The quality of the evidence was low.Necrotising enterocolitis was significantly reduced in the ESA group compared with the placebo group (typical RR 0.69, 95% CI 0.52 to 0.91; typical RD -0.03, 95% CI -0.05 to -0.01; I = 0% for RR and 22% for RD (low heterogeneity); NNTB 33, 95% CI 20 to 100; 15 studies, 2639 infants). The quality of the evidence was moderate.Data show a reduction in 'Any neurodevelopmental impairment at 18 to 22 months' corrected age in the ESA group (typical RR 0.62, 95% CI 0.48 to 0.80; typical RD -0.08, 95% CI -0.12 to -0.04; NNTB 13, 95% CI 8 to 25. I = 76% for RR (high heterogeneity) and 66% for RD (moderate); 4 studies, 1130 infants). The quality of the evidence was low.Results reveal increased scores on the Bayley-II Mental Development Index (MDI) at 18 to 24 months in the ESA group (weighted mean difference (WMD) 8.22, 95% CI 6.52 to 9.92; I = 97% (high heterogeneity); 3 studies, 981 children). The quality of the evidence was low.The total volume of RBCs transfused per infant was reduced by 7 mL/kg. The number of RBC transfusions per infant was minimally reduced, but the number of donors to whom infants who were transfused were exposed was not significantly reduced. Data show no significant difference in risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.24, 95% CI 0.81 to 1.90; typical RD 0.01, 95% CI -0.02 to 0.04; I = 0% (no heterogeneity) for RR; I = 34% (low heterogeneity) for RD; 8 studies, 1283 infants). Mortality was not affected, but results show significant reductions in the incidence of intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL).
AUTHORS' CONCLUSIONS
Early administration of ESAs reduces the use of red blood cell (RBC) transfusions, the volume of RBCs transfused, and donor exposure after study entry. Small reductions are likely to be of limited clinical importance. Donor exposure probably is not avoided, given that all but one study included infants who had received RBC transfusions before trial entry. This update found no significant difference in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age, which has been a topic of concern in earlier versions of this review. Early EPO treatment significantly decreased rates of IVH, PVL, and NEC. Neurodevelopmental outcomes at 18 to 22 months and later varied in published studies. Ongoing research should evaluate current clinical practices that will limit donor exposure. Promising but conflicting results related to the neuro protective effect of early EPO require further study. Very different results from the two largest published trials and high heterogeneity in the analyses indicate that we should wait for the results of two ongoing large trials before drawing firm conclusions. Administration of EPO is not currently recommended because limited benefits have been identified to date. Use of darepoetin requires further study.
Topics: Anemia, Neonatal; Darbepoetin alfa; Enterocolitis, Necrotizing; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Retinopathy of Prematurity
PubMed: 29145693
DOI: 10.1002/14651858.CD004863.pub5 -
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 -
The Cochrane Database of Systematic... Oct 2017Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO).
OBJECTIVES
To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes.
STATISTICS
for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis.
MAIN RESULTS
Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes.
AUTHORS' CONCLUSIONS
Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.
Topics: Bronchopulmonary Dysplasia; Humans; Infant, Newborn; Infant, Premature; Intermittent Positive-Pressure Ventilation; Pressure; Randomized Controlled Trials as Topic; Tidal Volume
PubMed: 29039883
DOI: 10.1002/14651858.CD003666.pub4 -
PloS One 2017Although investigators have implicated hypoxic-ischemia (HI) as a potential cause of periventricular leukomalacia (PVL), the role of clinical risk factors or markers for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although investigators have implicated hypoxic-ischemia (HI) as a potential cause of periventricular leukomalacia (PVL), the role of clinical risk factors or markers for HI in the development of PVL remains controversial. The aim of this study was to identify perinatal HI-related factors associated with PVL.
METHOD
The PubMed, EMBASE, and Cochrane Library databases were searched. The last search was performed on January 2017. Summary effect estimates (pooled odds ratios [ORs]) were calculated for each risk factor using fixed or random effects models with tests for heterogeneity and publication bias.
RESULTS
Fifteen studies with a total of 12,851 participants were included in this meta-analysis, and 14 potential risk factors were analyzed. The pooled results showed that mothers with oligohydramnios (OR, 1.55; 95% confidence interval [CI], 1.05 to 2.30), preterm infants with acidemia (OR, 1.87; 95% CI, 1.18 to 2.97), 1-minute Apgar score <7 (OR 2.69; 95% CI, 1.13 to 6.41), 5-minute Apgar score <7 (OR, 1.89; 95% CI, 1.39 to 2.56), apnea (OR, 1.76; 95% CI, 1.07 to 2.90), respiratory distress syndrome (OR, 1.46; 95% CI, 1.04 to 2.03), and seizures (OR, 4.60; 95% CI, 2.84 to 7.46) were associated with increased risk of PVL.
CONCLUSION
This study identified perinatal HI-related risk factors for the development of PVL in preterm infants. Future large-scale prospective clinical studies are required to validate and extend these findings.
Topics: Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leukomalacia, Periventricular; Pregnancy; Risk Factors
PubMed: 28931047
DOI: 10.1371/journal.pone.0184993