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International Journal of Clinical... Nov 2021To compare and evaluate the efficacy and safety of immediate cord clamping (ICC) and delayed cord clamping (DCC) in preterm infants. We performed a comprehensive and... (Meta-Analysis)
Meta-Analysis
To compare and evaluate the efficacy and safety of immediate cord clamping (ICC) and delayed cord clamping (DCC) in preterm infants. We performed a comprehensive and systematic meta-analysis of randomised controlled trials (RCTs) assessing ICC and DCC in preterm infants by searching PUBMED, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Database (from inception to 30 September 2020). Summary odds ratios or mean differences with 95% confidence intervals were calculated using a fixed- or random-effect model. A total of 20 RCTs with 1807 preterm infants were included in the study. DCC provided more benefits in increasing the haematocrit and haemoglobin levels at 24 hours of life (%), thus reducing the incidence of anaemia, necrotising enterocolitis, length of hospital stay and mortality than when ICC was performed. No significant differences were found between ICC and DCC in terms of peak bilirubin level; need for blood transfusion, mechanical ventilation (MV) and phototherapy; duration of MV and phototherapy; and incidences of intraventricular haemorrhage, retinopathy of prematurity, patent ductus arteriosus, respiratory distress syndrome, sepsis, jaundice, polycythaemia, periventricular leukomalacia and bronchopulmonary dysplasia. DCC is a safe, beneficial and feasible intervention for preterm infants. However, rigorously designed and large-scale RCTs are necessary to identify the role and ideal timing of DCC.
Topics: Anemia; Blood Transfusion; Cerebral Hemorrhage; Constriction; Humans; Infant; Infant, Newborn; Infant, Premature
PubMed: 34370357
DOI: 10.1111/ijcp.14709 -
Archives of Gynecology and Obstetrics Apr 2024The mode of delivery for twins born before 32 weeks of gestation remains controversial. Our purpose is to conduct a meta-analysis of twin pregnancies less than... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The mode of delivery for twins born before 32 weeks of gestation remains controversial. Our purpose is to conduct a meta-analysis of twin pregnancies less than 32 weeks or twin weight less than 1500 g, so as to find a suitable delivery mode.
METHODS
We searched PubMed database, Cochrane Library database, and EMBASE database through December 2022. This protocol was registered with PROSPERO (CRD42023386946) prior to initiation. Studies that compared vaginal delivery to cesarean section for newborns less than 32 weeks of gestation or birthweight under 1500 g were included. The primary result was neonatal mortality rate. Secondary result was neonatal morbidity. The quality of literatures included in the research was evaluated in accordance with Newcastle-Ottawa Scale (NOS) literature quality evaluation scale. We use odds ratio (OR) as the effect index for binary variables. Point estimates and 95% confidence intervals (95% CI) were calculated. P < 0. 05 indicated statistically significant difference.
RESULTS
Our search generated 5310 articles, and a total of 8 articles comprising a total of 14,703 newborns were included in the analysis. The odds ratios of neonatal mortality rate were for twins delivered by vaginal delivery compared to cesarean section were 0.84 (95% CI 0.57-1.24, P = 0.38). The 5-min Apgar score < 7 (95% CI 0.44-1.75, P = 0.72), necrotizing enterocolitis (95% CI 0.81-1.19, P = 0.82), intraventricular hemorrhage (95% CI 0.41-1.86, P = 0.71), periventricular leukomalacia (95% CI 0.16-4.52, P = 0.84), bronchopulmonary dysplasia (95% CI 0.88-1.36, P = 0.42), and respiratory distress syndrome (95% CI 0.23-2.01, P = 0.48) were not statistically significant between the two groups.
CONCLUSION
We have observed that vaginal delivery does not confer an increased risk of neonatal morbidity and mortality in twins born before 32 weeks of gestation. However, the current results are affected by substantial heterogeneity and confounding factors. We still need high-quality randomized-controlled studies require to address this important question.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Cesarean Section; Birth Weight; Delivery, Obstetric; Twins; Pregnancy, Twin
PubMed: 38066342
DOI: 10.1007/s00404-023-07307-y -
Archives of Disease in Childhood. Fetal... May 2021The association between maternal diabetes and outcomes of infants who are born preterm is unclear. (Meta-Analysis)
Meta-Analysis
CONTEXT
The association between maternal diabetes and outcomes of infants who are born preterm is unclear.
OBJECTIVE
To perform a systematic review and meta-analysis of clinical studies exploring the association between maternal diabetes and preterm infant outcomes.
METHODS
Medline, PubMed and Cumulative Index of Nursing and Allied Health Literature databases were searched without language restriction from 1 January 2000 until 19 August 2019. Studies examining preterm infants <37 weeks gestational age and reporting prespecified outcomes of this review based on maternal diabetes as primary exposure variable were included.
RESULTS
Of 7956 records identified through database searches, 9 studies were included in the study. No significant association was found between maternal diabetes and in-hospital mortality (adjusted RR (aRR) 0.90 (95% CI 0.73 to 1.11); 6 studies; participants=1 191 226; I=83%). Similarly, no significant association was found between maternal diabetes and bronchopulmonary dysplasia (aRR 1.00 (95% CI 0.92 to 1.07); 4 studies; participants=107 902; I=0%), intraventricular haemorrhage or cystic periventricular leukomalacia (aRR 0.91 (95% CI 0.80 to 1.03); 3 studies; participants=115 050; I=0%), necrotising enterocolitis (aRR 1.13 (95% CI 0.90 to 1.42); 5 studies; participants=142 579; I=56%) and retinopathy of prematurity (ROP) (aRR 1.17 (95% CI 0.85 to 1.61); 5 studies; participants=126 672; I=84). A sensitivity analysis where low risk of bias studies were included in the meta-analyses showed similar results; however, the heterogeneity was lower for in-hospital mortality and ROP.
CONCLUSION
Maternal diabetes was not associated with in-hospital mortality and severe neonatal morbidities in preterm infants. Future studies should explore the association between the severity of maternal diabetes with preterm infant outcomes.
Topics: Adult; Correlation of Data; Female; Hospital Mortality; Humans; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pregnancy; Pregnancy in Diabetics; Severity of Illness Index
PubMed: 33172874
DOI: 10.1136/archdischild-2020-320054 -
Developmental Medicine and Child... Jun 2016There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW:... (Review)
Review
AIM
There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW: ≤1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children born VPT/VLBW.
METHOD
A systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment in VPT/VLBW children (registration number CRD42014006943). Twenty-eight studies for motor outcomes were identified.
RESULTS
There was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non-use of antenatal steroids, were prognostic factors for CP. Male sex and gestational age were of limited use as prognostic factors for CP in cohorts restricted to ≤32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment.
INTERPRETATION
This review has identified factors which may be of prognostic value for CP and motor impairment in VPT/VLBW children and will help to form the basis of future prognostic research.
Topics: Cerebral Palsy; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Movement Disorders
PubMed: 26862030
DOI: 10.1111/dmcn.12972 -
The Cochrane Database of Systematic... Sep 2017Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous... (Review)
Review
BACKGROUND
Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies.
OBJECTIVES
To evaluate the benefits and harms of interventions that attempt to alter cerebral oxygenation guided by cerebral NIRS monitoring in order to prevent cerebral injury, improve neurological outcome, and increase survival in preterm infants born more than 8 weeks preterm.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 8), MEDLINE via PubMed (1966 to 10 September 2016), Embase (1980 to 10 September 2016), and CINAHL (1982 to 10 September 2016). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised clinical trials and quasi-randomised studies.
SELECTION CRITERIA
Randomised clinical trials and quasi-randomised clinical studies comparing continuous cerebral NIRS monitoring for at least 24 hours versus blinded NIRS or versus no NIRS monitoring.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected, assessed the quality of, and extracted data from the included trials and studies. If necessary, we contacted authors for further information. We conducted assessments of risks of bias; risks of design errors; and controlled the risks of random errors with Trial Sequential Analysis. We assessed the quality of the evidence with GRADE.
MAIN RESULTS
One randomised clinical trial met inclusion criteria, including infants born more than 12 weeks preterm. The trial employed adequate methodologies and was assessed at low risk of bias. One hundred and sixty-six infants were randomised to start continuous cerebral NIRS monitoring less than 3 hours after birth until 72 hours after birth plus appropriate interventions if NIRS was out of normal range according to a guideline versus conventional monitoring with blinded NIRS. There was no effect of NIRS plus guideline of mortality until term-equivalent age (RR 0.50, 95% CI 0.29 to 1.00; one trial; 166 participants). There were no effects of NIRS plus guideline on intraventricular haemorrhages: all grades (RR 0.93, 95% CI 0.65 to 1.34; one trial; 166 participants); grade III/IV (RR 0.57, 95% CI 0.25 to 1.31; one trial; 166 participants); and cystic periventricular leukomalacia (which did not occur in either group). Likewise, there was no effect of NIRS plus guideline on the occurrence of a patent ductus arteriosus (RR 1.96, 95% CI 0.94 to 4.08; one trial; 166 participants); chronic lung disease (RR 1.27, 95% CI 0.94 to 1.50; one trial; 166 participants); necrotising enterocolitis (RR 0.83, 95% CI 0.33 to 1.94; one trial; 166 participants); and retinopathy of prematurity (RR 1.64, 95% CI 0.75 to 3.00; one trial; 166 participants). There were no serious adverse events in any of the intervention groups. NIRS plus guideline caused more skin marks from the NIRS sensor in the control group than in the experimental group (unadjusted RR 0.31, 95% CI 0.10 to 0.92; one trial; 166 participants). There are no data regarding neurodevelopmental outcome, renal impairment or air leaks.The quality of evidence for all comparisons discussed above was assessed as very low apart from all-cause mortality and adverse events: these were assessed as low and moderate, respectively. The validity of all comparisons is hampered by a small sample of randomised infants, risk of bias due to lack of blinding, and indirectness of outcomes.
AUTHORS' CONCLUSIONS
The only eligible randomised clinical trial did not demonstrate any consistent effects of NIRS plus a guideline on the assessed clinical outcomes. The trial was, however, only powered to detect difference in cerebral oxygenation, not morbidities or mortality. Our systematic review did not reach sufficient power to prove or disprove effects on clinical outcomes. Further randomised clinical trials with low risks of bias and low risks of random errors are needed.
Topics: Brain; Brain Injuries; Humans; Infant, Extremely Premature; Infant, Newborn; Oxygen Consumption; Randomized Controlled Trials as Topic; Spectroscopy, Near-Infrared
PubMed: 28869278
DOI: 10.1002/14651858.CD011506.pub2 -
BMC Pregnancy and Childbirth Nov 2017Given the controversy around mode of delivery, our objective was to assess the evidence regarding the safest mode of delivery for actively resuscitated extremely preterm... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given the controversy around mode of delivery, our objective was to assess the evidence regarding the safest mode of delivery for actively resuscitated extremely preterm cephalic/non-cephalic twin pairs before 28 weeks of gestation.
METHODS
We searched Cochrane CENTRAL, MEDLINE, EMBASE and http://clinicaltrials.gov from January 1994 to January 2017. Two reviewers independently screened titles, abstracts and full text articles, extracted data and assessed risk of bias. We included randomized controlled trials and observational studies. Our primary outcome was a composite of neonatal death (<28 days of life) and severe brain injury in survivors (intraventricular hemorrhage grade ≥ 3 or periventricular leukomalacia). We performed random-effects meta-analyses, generating odds ratios with 95% confidence intervals for the first and second twin separately, and for both twins together. We assessed the risk of bias using a modified Newcastle Ottawa Scale (NOS) for observational studies and used Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).
RESULTS
Our search generated 2695 articles, and after duplicate removal, we screened 2051 titles and abstracts, selecting 113 articles for full-text review. We contacted 36 authors, and ultimately, three observational studies met our inclusion criteria. In cephalic/non-cephalic twin pairs delivered by caesarean section compared to vaginal birth at 24-27 weeks the odds ratio for our composite outcome of neonatal death and severe brain injury for the cephalic first twin was 0.35 (95% CI 0.00-92.61, two studies, I = 76%), 1.69 for the non-cephalic second twin (95% CI 0.04-72.81, two studies, I = 55%) and 0.83 for both twins (95% CI 0.05-13.43, two studies, I = 56%). According to the modified Newcastle Ottawa Scale we assessed individual study quality as being at high risk of bias and according to GRADE the overall evidence for our primary outcomes was very low.
CONCLUSION
Our systematic review on the safest mode of delivery for extremely preterm cephalic/non-cephalic twin pairs found very limited existing evidence, without significant differences in neonatal death and severe brain injury by mode of delivery.
Topics: Adult; Brain Injuries, Traumatic; Breech Presentation; Cesarean Section; Delivery, Obstetric; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Perinatal Death; Pregnancy; Pregnancy, Twin; Twins; Version, Fetal; Young Adult
PubMed: 29187166
DOI: 10.1186/s12884-017-1554-7 -
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... 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 -
The Cochrane Database of Systematic... Jun 2017Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.
OBJECTIVES
Primary objective 1. To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates Secondary objectives 1. To determine the effects of lactoferrin supplementation to enteral feeds to prevent neonatal sepsis and/or NEC on duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later2. To determine the adverse effects of lactoferrin supplementation for prophylaxis of neonatal sepsis and/or NECWhen data were available, we analyzed the following subgroups.1. Gestational age < 32 weeks and 32 to 36 weeks2. Birth weight < 1000 g (extremely low birth weight (ELBW) infants) and birth weight < 1500 g (very low birth weight (VLBW) infants)3. Type of feeding: breast milk versus formula milk SEARCH METHODS: We used the search strategy of the Cochrane Neonatal Review Group (CNRG) to update our search in December 2016. We searched the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), as well as trial registries and conference proceedings.
SELECTION CRITERIA
Randomized controlled trials (RCTs) evaluating oral lactoferrin at any dose or duration to prevent sepsis or NEC in preterm neonates.
DATA COLLECTION AND ANALYSIS
Review authors used standard methods of the CNRG.
MAIN RESULTS
This review includes six RCTs. Trial results show that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical risk ratio (RR) 0.59, 95% confidence interval (CI) 0.40 to 0.87; typical risk difference (RD) -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 17, 95% CI 10 to 50; six trials, 886 participants; low-quality evidence) and NEC stage II or III (typical RR 0.40, 95% CI 0.18 to 0.86; typical RD -0.04, 95% CI -0.06 to -0.01; NNTB 25, 95% CI 17 to 100; four studies, 750 participants; low-quality evidence). Lactoferrin supplementation did not have an effect on "all-cause mortality" (typical RR 0.65, 95% CI 0.37 to 1.11; typical RD -0.02, 95% CI -0.05 to 0; six studies, 1041 participants; low-quality evidence).Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.27, 95% CI 0.12 to 0.60; RD -0.13, 95% CI -0.19 to -0.06; NNTB 8, 95% CI 5 to 17; one study, 321 participants; low-quality evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; one study, 496 participants; low-quality evidence), but not "all-cause mortality" (low-quality evidence).Lactoferrin supplementation to enteral feeds with or without probiotics decreased bacterial and fungal sepsis but not CLD or length of hospital stay (low-quality evidence). Investigators reported no adverse effects and did not evaluate long-term neurological outcomes and PVL.
AUTHORS' CONCLUSIONS
Evidence of low quality suggests that lactoferrin supplementation to enteral feeds with or without probiotics decreases late-onset sepsis and NEC stage II or III in preterm infants without adverse effects. Completed ongoing trials will provide data from more than 6000 preterm neonates, which may enhance the quality of the evidence. Clarification regarding optimal dosing regimens, types of lactoferrin (human or bovine), and long-term outcomes is needed.
Topics: Administration, Oral; Bacterial Infections; Cause of Death; Chronic Disease; Enteral Nutrition; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lacticaseibacillus rhamnosus; Lactoferrin; Lung Diseases; Mycoses; Numbers Needed To Treat; Probiotics; Randomized Controlled Trials as Topic; Retinopathy of Prematurity; Sepsis
PubMed: 28658720
DOI: 10.1002/14651858.CD007137.pub5 -
American Journal of Obstetrics and... Feb 2021The objective of this study was to provide a systematic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to provide a systematic review and meta-analysis to quantify prognosis and identify factors associated with variations in reported mortality estimates among infants who were born at 22 weeks of gestation and provided proactive treatment (resuscitation and intensive care).
DATA SOURCES
PubMed, Scopus, and Web of Science databases, with no language restrictions, were searched for articles published from January 2000 to February 2020.
STUDY ELIGIBILITY CRITERIA
Reports on live-born infants who were delivered at 22 weeks of gestation and provided proactive care were included. The primary outcome was survival to hospital discharge; secondary outcomes included survival without major morbidity and survival without neurodevelopmental impairment. Because we expected differences across studies in the definitions for various morbidities, multiple definitions for composite outcomes of major morbidities were prespecified. Neurodevelopmental impairment was based on Bayley Scales of Infant Development II or III. Data extractions were performed independently, and outcomes agreed on a priori.
STUDY APPRAISAL AND SYNTHESIS METHODS
Methodological quality was assessed using the Quality in Prognostic Studies tool. An adapted version of the Grading of Recommendations Assessment, Development and Evaluation approach for prognostic studies was used to evaluate confidence in overall estimates. Outcomes were assessed as prevalence and 95% confidence intervals. Variabilities across studies attributable to heterogeneity were estimated with the I statistic; publication bias was assessed with the Luis Furuya-Kanamori index. Data were pooled using the inverse variance heterogeneity model.
RESULTS
Literature searches returned 21,952 articles, with 2034 considered in full; 31 studies of 2226 infants who were delivered at 22 weeks of gestation and provided proactive neonatal treatment were included. No articles were excluded for study design or risk of bias. The pooled prevalence of survival was 29.0% (95% confidence interval, 17.2-41.6; 31 studies, 2226 infants; I=79.4%; Luis Furuya-Kanamori index=0.04). Survival among infants born to mothers receiving antenatal corticosteroids was twice the survival of infants born to mothers not receiving antenatal corticosteroids (39.0% vs 19.5%; P<.01). The overall prevalence of survival without major morbidity, using a definition that includes any bronchopulmonary dysplasia, was 11.0% (95% confidence interval, 8.0-14.3; 10 studies, 374 infants; I=0%; Luis Furuya-Kanamori index=3.02). The overall rate of survival without moderate or severe impairment was 37.0% (95% confidence interval, 14.6-61.5; 5 studies, 39 infants; I=45%; Luis Furuya-Kanamori index=-0.15). Based on the year of publication, survival rates increased between 2000 and 2020 (slope of the regression line=0.09; standard error=0.03; P<.01). Studies were highly diverse with regard to interventions and outcomes reported.
CONCLUSION
The reported survival rates varied greatly among studies and were likely influenced by combining observational data from disparate sources, lack of individual patient-level data, and bias in the component studies from which the data were drawn. Therefore, pooled results should be interpreted with caution. To answer fundamental questions beyond the breadth of available data, multicenter, multidisciplinary collaborations, including alignment of important outcomes by stakeholders, are needed.
Topics: Adrenal Cortex Hormones; Bronchopulmonary Dysplasia; Cerebral Intraventricular Hemorrhage; Enterocolitis, Necrotizing; Fetal Viability; Gestational Age; Humans; Infant, Extremely Premature; Infant, Newborn; Intensive Care, Neonatal; Leukomalacia, Periventricular; Neurodevelopmental Disorders; Prenatal Care; Resuscitation; Retinopathy of Prematurity; Severity of Illness Index; Survival Rate
PubMed: 32745459
DOI: 10.1016/j.ajog.2020.07.051