Meta-Analysis
doi: 10.1002/14651858.CD005949.pub2.
Higher versus lower amino acid intake in parenteral nutrition for newborn infants
Affiliations
- PMID: 29505664
- PMCID: PMC6494253
- DOI: 10.1002/14651858.CD005949.pub2
Item in Clipboard
Meta-Analysis
Higher versus lower amino acid intake in parenteral nutrition for newborn infants
Cochrane Database Syst Rev.
.
Abstract
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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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.
Conflict of interest statement
None.
Figures
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Funnel plot of comparison: 1 Higher versus lower amino acid intake in parenteral nutrition, outcome: 1.1 Mortality to hospital discharge.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 1 Mortality to hospital discharge.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 2 Neurodevelopmental disability.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 3 Postnatal growth failure at discharge (weight < 10th centile).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 4 Postnatal growth failure at discharge (weight 2 SD below mean).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 5 Postnatal growth failure post discharge.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 6 Days to regain birth weight.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 7 Maximal weight loss (grams).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 8 Maximal weight loss %.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 9 Weight gain g/kg/d.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 10 Linear growth cm/week.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 11 Head circumference growth cm/week.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 12 Weight change z‐score.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 13 Head circumference change z‐score.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 14 Weight (grams).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 15 Length (cm).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 16 Head circumference (cm).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 17 Weight z‐score.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 18 Length z‐score.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 19 Head circumference z‐score.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 20 Days to full enteral feeds.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 21 Late‐onset sepsis.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 22 Necrotising enterocolitis.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 23 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 24 Patent ductus arteriosus.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 25 Intraventricular haemorrhage.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 26 Severe intraventricular haemorrhage.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 27 Periventricular leukomalacia.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 28 Retinopathy of prematurity.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 29 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 30 Cerebral palsy.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 31 Developmental delay at ≥ 18 months.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 32 Blindness.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 33 Deafness.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 34 Bayley MDI at ≥ 18 months.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 35 Bayley III score at ≥ 18 months.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 36 Bayley PDI at ≥ 18 months.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 37 Autism.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 38 Nitrogen balance.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 39 Protein balance.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 40 Abnormal serum ammonia.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 41 Abnormal blood urea nitrogen (various criteria).
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 42 Maximum blood urea nitrogen mmol/L.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 43 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 44 Hyperglycaemia treated with insulin.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 45 Hypoglycaemia.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 46 Metabolic acidosis.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 47 Cholestasis.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 48 Hyperkalaemia.
Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 49 Discontinued PN owing to biochemical intolerance.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 1 Mortality before hospital discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 2 Neurodevelopmental disability.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 3 Postnatal growth failure at discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 4 Postnatal growth failure post discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 5 Days to regain birth weight.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 6 Maximal weight loss (grams).
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 7 Maximal weight loss %.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 8 Weight gain g/kg/day to 1 month age.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 9 Weight gain g/kg/day to discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 10 Linear growth cm/week to 1 month age.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 11 Head circumference growth cm/week to 1 month age.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 12 Head circumference growth cm/week to discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 13 Weight change z‐score to 1 month age.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 14 Weight change z‐score to discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 15 Weight change z‐score post discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 16 Head circumference change z‐score to 1 month age.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 17 Head circumference change z‐score to discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 18 Head circumference change z‐score post discharge.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 19 Days to full enteral feeds.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 20 Late‐onset sepsis.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 21 Necrotising enterocolitis.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 22 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 23 Patent ductus arteriosus.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 24 Intraventricular haemorrhage.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 25 Severe intraventricular haemorrhage.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 26 Periventricular leukomalacia.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 27 Retinopathy of prematurity.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 28 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 29 Cerebral palsy.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 30 Developmental delay at ≥ 18 months.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 31 Blindness.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 32 Deafness.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 33 Abnormal serum ammonia (> 100 μmol/L).
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 34 Abnormal blood urea nitrogen (various criteria).
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 35 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 36 Hyperglycaemia treated with insulin.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 37 Hypoglycaemia.
Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 38 Metabolic acidosis.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 1 Mortality before hospital discharge.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 2 Head circumference growth cm/week to 1 month.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 3 Head circumference change z‐score to 1 month.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 4 Days to regain birth weight.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 5 Days to full enteral feeds.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 6 Late‐onset sepsis.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 7 Necrotising enterocolitis.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 8 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 9 Patent ductus arteriosus.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 10 Severe intraventricular haemorrhage.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 11 Periventricular leukomalacia.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 12 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 13 Hyperglycaemia treated with insulin.
Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 14 Cholestasis.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 1 Mortality to hospital discharge.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 2 Days to regain birth weight.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 3 Maximal weight loss (grams).
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 4 Maximal weight loss %.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 5 Weight gain g/kg/day up to 1 month age.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 6 Weight gain g/kg/day to discharge.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 7 Linear growth cm/week up to 1 month age.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 8 Head circumference growth cm/week up to 1 month age.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 9 Head circumference growth cm/week to discharge.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 10 Days to full enteral feeds.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 11 Late‐onset sepsis.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 12 Necrotising enterocolitis.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 13 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 14 Patent ductus arteriosus.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 15 Intraventricular haemorrhage.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 16 Severe intraventricular haemorrhage.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 17 Periventricular leukomalacia.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 18 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 19 Cerebral palsy.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 20 Developmental delay at ≥ 18 months.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 21 Blindness.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 22 Abnormal serum ammonia.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 23 Abnormal blood urea nitrogen (various criteria).
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 24 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 25 Hyperglycaemia treated with insulin.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 26 Hypoglycaemia.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 27 Metabolic acidosis.
Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 28 Cholestasis.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 1 Mortality before hospital discharge.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 2 Days to regain birth weight.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 3 Maximal weight loss (grams).
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 4 Maximal weight loss %.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 5 Weight gain g/kg/day up to 1 month.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 6 Weight gain g/kg/day to discharge.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 7 Linear growth cm/week up to 1 month.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 8 Head circumference growth cm/week up to 1 month.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 9 Head circumference growth cm/week to discharge.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 10 Days to full enteral feeds.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 11 Late‐onset sepsis.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 12 Necrotising enterocolitis.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 13 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 14 Patent ductus arteriosus.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 15 Intraventricular haemorrhage.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 16 Severe intraventricular haemorrhage.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 17 Periventricular leukomalacia.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 18 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 19 Cerebral palsy.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 20 Developmental delay at ≥ 18 months.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 21 Blindness.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 22 Abnormal serum ammonia.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 23 Abnormal blood urea nitrogen (various criteria).
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 24 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 25 Hyperglycaemia treated with insulin.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 26 Hypoglycaemia.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 27 Metabolic acidosis.
Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 28 Cholestasis.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 1 Mortality to hospital discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 2 Neurodevelopmental disability.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 3 Postnatal growth failure at discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 4 Days to regain birth weight.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 5 Maximal weight loss (grams).
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 6 Maximal weight loss %.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 7 Weight gain g/kg/day up to 1 month.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 8 Weight gain g/kg/day to discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 9 Linear growth cm/week up to 1 month.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 10 Linear growth cm/week to discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 11 Head circumference growth cm/week up to 1 month.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 12 Head circumference growth cm/week to discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 13 Weight change z‐score to discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 14 Head circumference change z‐score to 1 month.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 15 Head circumference change z‐score to discharge.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 16 Days to full enteral feeds.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 17 Late‐onset sepsis.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 18 Necrotising enterocolitis.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 19 Chronic lung disease ≥ 36 weeks' PMA.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 20 Intraventricular haemorrhage.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 21 Severe intraventricular haemorrhage.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 22 Periventricular leukomalacia.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 23 Retinopathy of prematurity.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 24 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 25 Cerebral palsy.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 26 Developmental delay at ≥ 18 months.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 27 Blindness.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 28 Deafness.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 29 Abnormal serum ammonia.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 30 Abnormal blood urea nitrogen (various criteria).
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 31 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 32 Hyperglycaemia treated with insulin.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 33 Hypoglycaemia.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 34 Metabolic acidosis.
Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 35 Cholestasis.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 1 Mortality before hospital discharge.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 2 Neurodevelopmental disability.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 3 Postnatal growth failure.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 4 Days to regain birth weight.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 5 Maximal weight loss (grams).
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 6 Maximal weight loss %.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 7 Weight gain g/kg/day.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 8 Linear growth cm/week.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 9 Head circumference growth cm/week.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 10 Weight change z‐score.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 11 Head circumference change z‐score.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 12 Days to full enteral feeds.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 13 Late‐onset sepsis.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 14 Necrotising enterocolitis.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 15 Chronic lung disease ≥ 36 weeks' PMA.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 16 Intraventricular haemorrhage.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 17 Severe intraventricular haemorrhage.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 18 Periventricular leukomalacia.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 19 Retinopathy of prematurity.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 20 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 21 Cerebral palsy.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 22 Developmental delay at ≥ 18 months.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 23 Blindness.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 24 Deafness.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 25 Abnormal serum ammonia > 122 μmol/L.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 26 Abnormal blood urea nitrogen > 21.4 mmol/L.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 27 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 28 Hyperglycaemia treated with insulin.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 29 Hypoglycaemia.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 30 Metabolic acidosis.
Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 31 Cholestasis.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 1 Mortality before hospital discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 2 Neurodevelopmental disability.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 3 Postnatal growth failure at discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 4 Days to regain birth weight.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 5 Maximal weight loss (grams).
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 6 Maximal weight loss %.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 7 Weight gain g/kg/day up to 1 month.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 8 Weight gain g/kg/day to discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 9 Linear growth cm/week up to 1 month.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 10 Head circumference growth cm/week up to 1 month age.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 11 Head circumference growth cm/week to discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 12 Weight change z‐score to discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 13 Head circumference change z‐score to 1 month age.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 14 Head circumference change z‐score to discharge.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 15 Days to full enteral feeds.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 16 Late‐onset sepsis.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 17 Necrotising enterocolitis.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 18 Chronic lung disease ≥ 36 weeks' PMA.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 19 Intraventricular haemorrhage.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 20 Severe intraventricular haemorrhage.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 21 Periventricular leukomalacia.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 22 Retinopathy of prematurity.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 23 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 24 Cerebral palsy.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 25 Developmental delay at ≥ 18 months.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 26 Blindness.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 27 Deafness.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 28 Abnormal serum ammonia > 122 μmol/L.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 29 Abnormal blood urea nitrogen (various criteria).
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 30 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 31 Hyperglycaemia treated with insulin.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 32 Hypoglycaemia.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 33 Metabolic acidosis.
Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 34 Cholestasis.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 1 Mortality before hospital discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 2 Neurodevelopmental disability.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 3 Postnatal growth failure at discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 4 Days to regain birth weight.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 5 Maximal weight loss (grams).
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 6 Maximal weight loss %.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 7 Weight gain g/kg/day to 1 month.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 8 Weight gain g/kg/day to discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 9 Linear growth cm/week up to 1 month age.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 10 Head circumference growth cm/week up to 1 month age.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 11 Head circumference growth cm/week to discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 12 Weight change z‐score to 1 month.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 13 Weight change z‐score to discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 14 Weight change z‐score post discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 15 Head circumference change z‐score to 1 month.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 16 Head circumference change z‐score to discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 17 Head circumference change z‐score post discharge.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 18 Days to full enteral feeds.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 19 Late‐onset sepsis.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 20 Necrotising enterocolitis.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 21 Chronic lung disease ≥ 36 weeks' PMA.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 22 Patent ductus arteriosus.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 23 Intraventricular haemorrhage.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 24 Severe intraventricular haemorrhage.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 25 Periventricular leukomalacia.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 26 Retinopathy of prematurity.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 27 Severe retinopathy of prematurity > stage 2 or treated.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 28 Cerebral palsy.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 29 Developmental delay at ≥ 18 months.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 30 Blindness.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 31 Deafness.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 32 Abnormal serum ammonia.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 33 Abnormal blood urea nitrogen.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 34 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 35 Hyperglycaemia treated with insulin.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 36 Hypoglycaemia.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 37 Metabolic acidosis.
Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 38 Cholestasis.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 1 Mortality before hospital discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 2 Neurodevelopmental disability.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 3 Postnatal growth failure at discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 4 Postnatal growth failure post discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 5 Days to regain birth weight.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 6 Maximal weight loss (grams).
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 7 Maximal weight loss %.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 8 Weight gain g/kg/day up to 1 month age.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 9 Weight gain g/kg/day to discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 10 Linear growth cm/week up to 1 month age.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 11 Head circumference growth cm/week up to 1 month age.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 12 Head circumference growth cm/week to discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 13 Weight change z‐score up to 1 month age.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 14 Weight change z‐score to discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 15 Weight change z‐score post discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 16 Head circumference change z‐score up to 1 month.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 17 Head circumference change z‐score to discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 18 Head circumference change z‐score post discharge.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 19 Days to full enteral feeds.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 20 Late‐onset sepsis.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 21 Necrotising enterocolitis.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 22 Chronic lung disease at ≥ 36 weeks' PMA.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 23 Intraventricular haemorrhage.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 24 Severe intraventricular haemorrhage.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 25 Periventricular leukomalacia.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 26 Retinopathy of prematurity.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 27 Severe retinopathy of prematurity (> stage 2 or treated).
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 28 Cerebral palsy.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 29 Developmental delay at ≥ 18 months.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 30 Blindness.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 31 Deafness.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 32 Abnormal serum ammonia > 122 μmol/L.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 33 Abnormal blood urea nitrogen.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 34 Hyperglycaemia, plasma glucose > 8.3 mmol/L.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 35 Hyperglycaemia treated with insulin.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 36 Hypoglycaemia.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 37 Metabolic acidosis.
Comparison 10 Higher versus lower amino acid intake in parenteral nutrition: sensitivity analysis (allocation concealment, adequate randomisation, blinding of treatment, less than 10% loss to follow‐up), Outcome 38 Cholestasis.
Comment in
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Commentary on "Higher versus Lower Amino Acid Intake in Parenteral Nutrition for Newborn Infants".Neonatology. 2019;116(1):92-96. doi: 10.1159/000495913. Epub 2019 May 23. Neonatology. 2019. PMID: 31121599 No abstract available.
References
References to studies included in this review
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Hata 2002 {published data only}
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Kashyap 2007 {published data only}
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Liu 2015 {published data only}
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Makay 2007 {published data only}
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Morgan 2014 {published data only}
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Tan 2008 {published data only}
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- Burgess L, Morgan C, Mayes K, Tan M. Plasma arginine levels and blood glucose control in very preterm infants receiving 2 different parenteral nutrition regimens. Journal of Parenteral and Enteral Nutrition 2014;38(2):243‐53. - PubMed
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- Tan MJ, Cooke RW. Improving head growth in very preterm infants ‐ a randomised controlled trial I: neonatal outcomes. Archives of Disease in Childhood. Fetal and Neonatal Edition 2008;93(5):F337‐41. - PubMed
Tang 2009 {published data only}
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te Braake 2005 {published data only}
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- Braake FW, Schierbeek H, Groof K, Vermes A, Longini M, Buonocore G, at al. Glutathione synthesis rates after amino acid administration directly after birth in preterm infants. American Journal of Clinical Nutrition 2008;88(2):333‐9. - PubMed
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- Akker CH, Braake FW, Schierbeek H, Rietveld T, Wattimena DJ, Bunt JE, et al. Albumin synthesis in premature neonates is stimulated by parenterally administered amino acids during the first days of life. American Journal of Clinical Nutrition 2007;86(4):1003‐8. - PubMed
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- Akker CH, Braake FW, Weisglas‐Kuperus N, Goudoever JB. Observational outcome results following a randomized controlled trial of early amino acid administration in preterm infants. Journal of Pediatric Gastroenterology and Nutrition 2014;59(6):714‐9. - PubMed
Thureen 2003 {published data only}
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- Thureen PJ, Melara D, Fennessey PV, Hay Jr WW. Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period. Pediatric Research 2003;53:24‐32. - PubMed
Uthaya 2016 {published data only}
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- Uthaya S, Liu X, Babalis D, Dore CJ, Warwick J, Bell J, et al. Nutritional evaluation and optimisation in neonates: a randomized, double‐blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition. American Journal of Clinical Nutrition 2016;103:1443‐52. - PMC - PubMed
Vaidya 1995 {published data only}
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- Vaidya UV, Bhave SA, Pandit AN. Parenteral nutrition (PN) in the management of very low birth weight (VLBW) babies ‐ a randomized controlled trial. Indian Pediatrics 1995;32(2):165‐70. - PubMed
van Goudoever 1995 {published data only}
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- Goudoever JB, Colen T, Wattimena JL, Huijmans JG, Carnielli VP, Sauer PJ. Immediate commencement of amino acid supplementation in preterm infants: effect on serum amino acid concentrations and protein kinetics on the first day of life. Journal of Pediatrics 1995;127(3):458‐65. - PubMed
van Lingen 1992 {published data only}
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- Lingen RA, Goudoever JB, Luijendijk IH, Wattimena JL, Sauer PJ. Effects of early amino acid administration during total parenteral nutrition on protein metabolism in pre‐term infants. Clinical Science 1992;82(2):199‐203. - PubMed
Vlaardingerbroek 2013 {published data only}
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- Roelants JA, Vlaardingerbroek H, Akker CH, Jonge RC, Goudoever JB, Vermeulen MJ. Two‐year follow‐up of a randomized controlled nutrition intervention trial in very low‐birth‐weight infants. Journal of Parenteral and Enteral Nutrition 2016 Nov 1:148607116678196. - PubMed
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- Vlaardingerbroek H, Roelants JA, Rook D, Dorst K, Schierbeek H, Vermes A, et al. Adaptive regulation of amino acid metabolism on early parenteral lipid and high‐dose amino acid administration in VLBW infants ‐ a randomized, controlled trial. Clinical Nutrition 2014;33(6):982‐90. - PubMed
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- Vlaardingerbroek H, Schierbeek H, Rook D, Vermeulen MJ, Dorst K, Vermes A, et al. Albumin synthesis in very low birth weight infants is enhanced by early parenteral lipid and high‐dose amino acid administration. Clinical Nutrition 2016;35(2):344‐50. - PubMed
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- Xie E, Sun J, Shen Y, Ju H, Li J, Zhang G, et al. Influence of early rapidly increased amino acid dosaging on nitrogen balance and growth in preterm infants. Chinese Journal of Clinical Nutrition 2014;22(3):136‐40.
References to studies excluded from this review
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McIntosh 1990 {published data only}
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