Higher versus lower amino acid intake in parenteral nutrition for newborn infants

David A Osborn; Tim Schindler; Lisa J Jones; John KH Sinn; Srinivas Bolisetty

doi:10.1002/14651858.CD005949.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Funnel plot of comparison: 1 Higher versus lower amino acid intake in parenteral nutrition, outcome: 1.1 Mortality to hospital discharge.

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Analysis 1.1

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 1 Mortality to hospital discharge.

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Analysis 1.2

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 2 Neurodevelopmental disability.

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Analysis 1.3

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 3 Postnatal growth failure at discharge (weight < 10th centile).

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Analysis 1.4

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 4 Postnatal growth failure at discharge (weight 2 SD below mean).

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Analysis 1.5

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 5 Postnatal growth failure post discharge.

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Analysis 1.6

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 6 Days to regain birth weight.

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Analysis 1.7

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 7 Maximal weight loss (grams).

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Analysis 1.8

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 8 Maximal weight loss %.

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Analysis 1.9

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 9 Weight gain g/kg/d.

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Analysis 1.10

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 10 Linear growth cm/week.

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Analysis 1.11

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 11 Head circumference growth cm/week.

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Analysis 1.12

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 12 Weight change z‐score.

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Analysis 1.13

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 13 Head circumference change z‐score.

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Analysis 1.14

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 14 Weight (grams).

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Analysis 1.15

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 15 Length (cm).

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Analysis 1.16

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 16 Head circumference (cm).

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Analysis 1.17

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 17 Weight z‐score.

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Analysis 1.18

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 18 Length z‐score.

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Analysis 1.19

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 19 Head circumference z‐score.

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Analysis 1.20

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 20 Days to full enteral feeds.

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Analysis 1.21

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 21 Late‐onset sepsis.

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Analysis 1.22

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 22 Necrotising enterocolitis.

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Analysis 1.23

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 23 Chronic lung disease at ≥ 36 weeks' PMA.

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Analysis 1.24

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 24 Patent ductus arteriosus.

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Analysis 1.25

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 25 Intraventricular haemorrhage.

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Analysis 1.26

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 26 Severe intraventricular haemorrhage.

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Analysis 1.27

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 27 Periventricular leukomalacia.

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Analysis 1.28

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 28 Retinopathy of prematurity.

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Analysis 1.29

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 29 Severe retinopathy of prematurity (> stage 2 or treated).

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Analysis 1.30

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 30 Cerebral palsy.

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Analysis 1.31

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 31 Developmental delay at ≥ 18 months.

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Analysis 1.32

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 32 Blindness.

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Analysis 1.33

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 33 Deafness.

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Analysis 1.34

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 34 Bayley MDI at ≥ 18 months.

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Analysis 1.35

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 35 Bayley III score at ≥ 18 months.

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Analysis 1.36

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 36 Bayley PDI at ≥ 18 months.

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Analysis 1.37

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 37 Autism.

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Analysis 1.38

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 38 Nitrogen balance.

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Analysis 1.39

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 39 Protein balance.

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Analysis 1.40

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 40 Abnormal serum ammonia.

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Analysis 1.41

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 41 Abnormal blood urea nitrogen (various criteria).

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Analysis 1.42

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 42 Maximum blood urea nitrogen mmol/L.

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Analysis 1.43

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 43 Hyperglycaemia, plasma glucose > 8.3 mmol/L.

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Analysis 1.44

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 44 Hyperglycaemia treated with insulin.

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Analysis 1.45

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 45 Hypoglycaemia.

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Analysis 1.46

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 46 Metabolic acidosis.

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Analysis 1.47

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 47 Cholestasis.

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Analysis 1.48

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 48 Hyperkalaemia.

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Analysis 1.49

Comparison 1 Higher versus lower amino acid intake in parenteral nutrition, Outcome 49 Discontinued PN owing to biochemical intolerance.

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Analysis 2.1

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 1 Mortality before hospital discharge.

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Analysis 2.2

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 2 Neurodevelopmental disability.

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Analysis 2.3

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 3 Postnatal growth failure at discharge.

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Analysis 2.4

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 4 Postnatal growth failure post discharge.

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Analysis 2.5

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 5 Days to regain birth weight.

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Analysis 2.6

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 6 Maximal weight loss (grams).

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Analysis 2.7

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 7 Maximal weight loss %.

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Analysis 2.8

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.

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Analysis 2.9

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.

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Analysis 2.10

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.

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Analysis 2.11

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.

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Analysis 2.12

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.

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Analysis 2.13

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.

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Analysis 2.14

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.

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Analysis 2.15

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.

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Analysis 2.16

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.

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Analysis 2.17

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.

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Analysis 2.18

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.

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Analysis 2.19

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 19 Days to full enteral feeds.

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Analysis 2.20

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 20 Late‐onset sepsis.

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Analysis 2.21

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 21 Necrotising enterocolitis.

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Analysis 2.22

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.

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Analysis 2.23

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 23 Patent ductus arteriosus.

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Analysis 2.24

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 24 Intraventricular haemorrhage.

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Analysis 2.25

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 25 Severe intraventricular haemorrhage.

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Analysis 2.26

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 26 Periventricular leukomalacia.

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Analysis 2.27

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 27 Retinopathy of prematurity.

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Analysis 2.28

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).

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Analysis 2.29

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 29 Cerebral palsy.

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Analysis 2.30

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 30 Developmental delay at ≥ 18 months.

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Analysis 2.31

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 31 Blindness.

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Analysis 2.32

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 32 Deafness.

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Analysis 2.33

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).

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Analysis 2.34

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).

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Analysis 2.35

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.

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Analysis 2.36

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 36 Hyperglycaemia treated with insulin.

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Analysis 2.37

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 37 Hypoglycaemia.

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Analysis 2.38

Comparison 2 Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake, Outcome 38 Metabolic acidosis.

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Analysis 3.1

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 1 Mortality before hospital discharge.

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Analysis 3.2

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.

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Analysis 3.3

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.

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Analysis 3.4

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.

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Analysis 3.5

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.

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Analysis 3.6

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 6 Late‐onset sepsis.

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Analysis 3.7

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 7 Necrotising enterocolitis.

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Analysis 3.8

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.

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Analysis 3.9

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 9 Patent ductus arteriosus.

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Analysis 3.10

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 10 Severe intraventricular haemorrhage.

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Analysis 3.11

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 11 Periventricular leukomalacia.

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Analysis 3.12

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).

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Analysis 3.13

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 13 Hyperglycaemia treated with insulin.

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Analysis 3.14

Comparison 3 Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 14 Cholestasis.

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Analysis 4.1

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.

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Analysis 4.2

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.

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Analysis 4.3

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).

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Analysis 4.4

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 %.

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Analysis 4.5

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.

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Analysis 4.6

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.

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Analysis 4.7

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.

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Analysis 4.8

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.

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Analysis 4.9

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.

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Analysis 4.10

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.

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Analysis 4.11

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.

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Analysis 4.12

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 12 Necrotising enterocolitis.

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Analysis 4.13

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.

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Analysis 4.14

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.

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Analysis 4.15

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 15 Intraventricular haemorrhage.

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Analysis 4.16

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.

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Analysis 4.17

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 17 Periventricular leukomalacia.

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Analysis 4.18

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).

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Analysis 4.19

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 19 Cerebral palsy.

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Analysis 4.20

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.

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Analysis 4.21

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 21 Blindness.

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Analysis 4.22

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.

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Analysis 4.23

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).

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Analysis 4.24

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.

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Analysis 4.25

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.

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Analysis 4.26

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 26 Hypoglycaemia.

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Analysis 4.27

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 27 Metabolic acidosis.

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Analysis 4.28

Comparison 4 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake, Outcome 28 Cholestasis.

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Analysis 5.1

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.

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Analysis 5.2

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.

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Analysis 5.3

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).

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Analysis 5.4

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 %.

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Analysis 5.5

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.

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Analysis 5.6

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.

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Analysis 5.7

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.

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Analysis 5.8

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.

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Analysis 5.9

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.

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Analysis 5.10

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.

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Analysis 5.11

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.

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Analysis 5.12

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 12 Necrotising enterocolitis.

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Analysis 5.13

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.

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Analysis 5.14

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.

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Analysis 5.15

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 15 Intraventricular haemorrhage.

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Analysis 5.16

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.

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Analysis 5.17

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 17 Periventricular leukomalacia.

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Analysis 5.18

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).

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Analysis 5.19

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 19 Cerebral palsy.

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Analysis 5.20

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.

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Analysis 5.21

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 21 Blindness.

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Analysis 5.22

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.

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Analysis 5.23

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).

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Analysis 5.24

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.

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Analysis 5.25

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.

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Analysis 5.26

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 26 Hypoglycaemia.

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Analysis 5.27

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 27 Metabolic acidosis.

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Analysis 5.28

Comparison 5 Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake, Outcome 28 Cholestasis.

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Analysis 6.1

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 1 Mortality to hospital discharge.

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Analysis 6.2

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 2 Neurodevelopmental disability.

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Analysis 6.3

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.

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Analysis 6.4

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.

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Analysis 6.5

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 5 Maximal weight loss (grams).

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Analysis 6.6

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 6 Maximal weight loss %.

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Analysis 6.7

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.

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Analysis 6.8

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.

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Analysis 6.9

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.

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Analysis 6.10

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.

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Analysis 6.11

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.

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Analysis 6.12

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.

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Analysis 6.13

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.

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Analysis 6.14

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.

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Analysis 6.15

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.

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Analysis 6.16

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.

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Analysis 6.17

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 17 Late‐onset sepsis.

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Analysis 6.18

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 18 Necrotising enterocolitis.

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Analysis 6.19

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.

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Analysis 6.20

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 20 Intraventricular haemorrhage.

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Analysis 6.21

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 21 Severe intraventricular haemorrhage.

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Analysis 6.22

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 22 Periventricular leukomalacia.

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Analysis 6.23

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 23 Retinopathy of prematurity.

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Analysis 6.24

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).

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Analysis 6.25

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 25 Cerebral palsy.

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Analysis 6.26

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.

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Analysis 6.27

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 27 Blindness.

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Analysis 6.28

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 28 Deafness.

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Analysis 6.29

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 29 Abnormal serum ammonia.

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Analysis 6.30

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).

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Analysis 6.31

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.

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Analysis 6.32

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 32 Hyperglycaemia treated with insulin.

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Analysis 6.33

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 33 Hypoglycaemia.

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Analysis 6.34

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 34 Metabolic acidosis.

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Analysis 6.35

Comparison 6 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance, Outcome 35 Cholestasis.

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Analysis 7.1

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.

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Analysis 7.2

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 2 Neurodevelopmental disability.

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Analysis 7.3

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 3 Postnatal growth failure.

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Analysis 7.4

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.

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Analysis 7.5

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).

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Analysis 7.6

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 6 Maximal weight loss %.

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Analysis 7.7

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.

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Analysis 7.8

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.

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Analysis 7.9

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.

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Analysis 7.10

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.

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Analysis 7.11

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.

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Analysis 7.12

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.

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Analysis 7.13

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 13 Late‐onset sepsis.

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Analysis 7.14

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 14 Necrotising enterocolitis.

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Analysis 7.15

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.

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Analysis 7.16

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 16 Intraventricular haemorrhage.

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Analysis 7.17

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 17 Severe intraventricular haemorrhage.

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Analysis 7.18

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 18 Periventricular leukomalacia.

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Analysis 7.19

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 19 Retinopathy of prematurity.

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Analysis 7.20

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).

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Analysis 7.21

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 21 Cerebral palsy.

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Analysis 7.22

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.

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Analysis 7.23

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 23 Blindness.

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Analysis 7.24

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 24 Deafness.

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Analysis 7.25

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.

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Analysis 7.26

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.

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Analysis 7.27

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.

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Analysis 7.28

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.

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Analysis 7.29

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 29 Hypoglycaemia.

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Analysis 7.30

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 30 Metabolic acidosis.

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Analysis 7.31

Comparison 7 Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants, Outcome 31 Cholestasis.

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Analysis 8.1

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 1 Mortality before hospital discharge.

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Analysis 8.2

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 2 Neurodevelopmental disability.

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Analysis 8.3

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 3 Postnatal growth failure at discharge.

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Analysis 8.4

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 4 Days to regain birth weight.

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Analysis 8.5

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 5 Maximal weight loss (grams).

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Analysis 8.6

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 6 Maximal weight loss %.

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Analysis 8.7

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.

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Analysis 8.8

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.

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Analysis 8.9

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.

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Analysis 8.10

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.

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Analysis 8.11

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.

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Analysis 8.12

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.

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Analysis 8.13

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.

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Analysis 8.14

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.

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Analysis 8.15

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 15 Days to full enteral feeds.

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Analysis 8.16

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 16 Late‐onset sepsis.

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Analysis 8.17

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 17 Necrotising enterocolitis.

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Analysis 8.18

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.

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Analysis 8.19

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 19 Intraventricular haemorrhage.

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Analysis 8.20

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 20 Severe intraventricular haemorrhage.

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Analysis 8.21

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 21 Periventricular leukomalacia.

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Analysis 8.22

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 22 Retinopathy of prematurity.

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Analysis 8.23

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).

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Analysis 8.24

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 24 Cerebral palsy.

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Analysis 8.25

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 25 Developmental delay at ≥ 18 months.

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Analysis 8.26

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 26 Blindness.

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Analysis 8.27

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 27 Deafness.

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Analysis 8.28

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.

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Analysis 8.29

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).

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Analysis 8.30

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.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.31

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 31 Hyperglycaemia treated with insulin.

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Analysis 8.32

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 32 Hypoglycaemia.

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Analysis 8.33

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 33 Metabolic acidosis.

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Analysis 8.34

Comparison 8 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement, Outcome 34 Cholestasis.

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Analysis 9.1

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 1 Mortality before hospital discharge.

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Analysis 9.2

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 2 Neurodevelopmental disability.

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Analysis 9.3

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 3 Postnatal growth failure at discharge.

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Analysis 9.4

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 4 Days to regain birth weight.

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Analysis 9.5

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 5 Maximal weight loss (grams).

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Analysis 9.6

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 6 Maximal weight loss %.

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Analysis 9.7

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.

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Analysis 9.8

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.

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Analysis 9.9

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.

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Analysis 9.10

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.

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Analysis 9.11

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.

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Analysis 9.12

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.

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Analysis 9.13

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 13 Weight change z‐score to discharge.

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Analysis 9.14

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 14 Weight change z‐score post discharge.

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Analysis 9.15

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.

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Analysis 9.16

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.

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Analysis 9.17

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.

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Analysis 9.18

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 18 Days to full enteral feeds.

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Analysis 9.19

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 19 Late‐onset sepsis.

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Analysis 9.20

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 20 Necrotising enterocolitis.

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Analysis 9.21

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 21 Chronic lung disease ≥ 36 weeks' PMA.

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Analysis 9.22

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 22 Patent ductus arteriosus.

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Analysis 9.23

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 23 Intraventricular haemorrhage.

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Analysis 9.24

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 24 Severe intraventricular haemorrhage.

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Analysis 9.25

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 25 Periventricular leukomalacia.

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Analysis 9.26

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 26 Retinopathy of prematurity.

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Analysis 9.27

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.

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Analysis 9.28

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 28 Cerebral palsy.

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Analysis 9.29

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 29 Developmental delay at ≥ 18 months.

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Analysis 9.30

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 30 Blindness.

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Analysis 9.31

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 31 Deafness.

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Analysis 9.32

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 32 Abnormal serum ammonia.

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Analysis 9.33

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 33 Abnormal blood urea nitrogen.

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Analysis 9.34

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.

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Analysis 9.35

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 35 Hyperglycaemia treated with insulin.

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Analysis 9.36

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 36 Hypoglycaemia.

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Analysis 9.37

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 37 Metabolic acidosis.

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Analysis 9.38

Comparison 9 Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake, Outcome 38 Cholestasis.

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Analysis 10.1

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.

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Analysis 10.2

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Analysis 10.3

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Analysis 10.4

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Analysis 10.5

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Analysis 10.6

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Analysis 10.7

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Analysis 10.8

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Analysis 10.9

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Analysis 10.10

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Analysis 10.11

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Analysis 10.12

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Analysis 10.13

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Analysis 10.14

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Analysis 10.15

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Analysis 10.16

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Analysis 10.17

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Analysis 10.18

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Analysis 10.19

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Analysis 10.20

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Analysis 10.21

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Analysis 10.22

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Analysis 10.23

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Analysis 10.24

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Analysis 10.25

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Analysis 10.26

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Analysis 10.27

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Analysis 10.28

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Analysis 10.29

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Analysis 10.30

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Analysis 10.31

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Analysis 10.32

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Analysis 10.33

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Analysis 10.34

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Analysis 10.35

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Analysis 10.36

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Analysis 10.37

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Analysis 10.38

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Summary of findings for the main comparison. Higher versus lower amino acid intake in parenteral nutrition for newborn infants

Higher versus lower amino acid intake in parenteral nutrition for newborn infants
Patient or population: preterm infants Settings: neonatal intensive care Intervention: higher versus lower amino acid intake in parenteral nutrition
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Higher vs lower amino acid intake in parenteral nutrition
Mortality to hospital discharge Follow‐up: to discharge	Study population		RR 0.9 (0.69 to 1.17)	1407 (14 studies)	⊕⊕⊝⊝ low^a,b	No significant differences found in subgroup analyses according to amino acid intake at commencement, at maximal intake, or at commencement and maximal intake; according to management of caloric balance (non‐protein caloric intake); in very preterm or very low birth weight infants; according to age of commencement; or according to timing of lipid intake Quality of evidence downgraded owing to imprecision and potential for publication or reporting bias
	131 per 1000	118 per 1000 (90 to 153)
	Moderate
	127 per 1000	114 per 1000 (88 to 149)
Neurodevelopmental disability Follow‐up: to discharge	Study population		RR 1.04 (0.48 to 2.23)	201 (2 studies)	⊕⊝⊝⊝ very low^a,b,c,d	Limited neurodevelopmental data. No significant differences found for any secondary outcome including cerebral palsy, developmental delay, blindness, deafness, Bayley Scales of Infant Development scores, or autism Quality of evidence downgraded owing to risk of bias, inconsistency, imprecision, and potential for publication or reporting bias
	118 per 1000	122 per 1000 (56 to 262)
	Moderate
	108 per 1000	112 per 1000 (52 to 241)
Postnatal growth failure at discharge (weight < 10th centile) Follow‐up: to discharge	Study population		RR 0.74 (0.56 to 0.97)	203 (3 studies)	⊕⊝⊝⊝ very low^b,e,f	Subgroup analyses found significant reduction in postnatal growth failure at discharge for infants commenced on high amino acid intake (> 2 to ≤ 3 g/kg/d) that increased amino acid and non‐protein caloric intake; commenced intake at < 24 hours' age; and provided early lipid infusion. Quality of evidence downgraded owing to risk of bias, imprecision, and potential for publication or reporting bias
	554 per 1000	410 per 1000 (310 to 538)
	Moderate
	684 per 1000	506 per 1000 (383 to 663)
Weight gain to discharge (g/kg/d)		Mean weight gain to discharge (g/kg/d) in intervention groups was 0.76 higher (0.02 lower to 1.54 higher).		291 (4 studies)	⊕⊝⊝⊝ very low^a,b,c	No significant subgroup effects found according to intake; timing of commencement; management of caloric balance; or timing of lipid intake Reduction in weight gain to 1 month age attributable to the effect of a single study (Balasubramanian 2013) that did not provide a lipid infusion Quality of evidence downgraded owing to risk of bias, imprecision, and potential for publication or reporting bias
Head circumference growth to discharge (cm/week) Follow‐up: to discharge		Mean head circumference growth to discharge (cm/week) in intervention groups was 0.09 higher (0.06 to 0.13 higher).		315 (4 studies)	⊕⊝⊝⊝ very low^b,c,d,f	Subgroup analyses found a significant increase in head circumference growth to discharge for infants on high amino acid intake (> 2 to ≤ 3 g/kg/d) at commencement; and for infants on high (> 3 to ≤ 4 g/kg/d) amino acid intake at maximal intake. All studies provided isocaloric non‐protein energy intake and early lipid infusion in both groups. Quality of evidence downgraded owing to risk of bias, inconsistency, imprecision, and potential for publication or reporting bias
Retinopathy of prematurity Follow‐up: to discharge	Study population		RR 0.44 (0.21 to 0.93)	269 (4 studies)	⊕⊝⊝⊝ very low^b,e,f	Subgroup analyses found reduction in retinopathy of prematurity in studies that commenced high (> 2 to ≤ 3 g/kg/d) amino acid intake; that increased amino acid and non‐protein caloric intake; in very preterm or very low birth weight infants; that commenced intake at < 24 hours' age; and provided early lipid infusion. Quality of evidence downgraded owing to risk of bias, imprecision, and potential for publication or reporting bias
	144 per 1000	63 per 1000 (30 to 134)
	Moderate
	179 per 1000	79 per 1000 (38 to 166)
Abnormal blood urea nitrogen (various criteria) Follow‐up: to discharge	Study population		RR 2.77 (2.13 to 3.61)	688 (7 studies)	⊕⊕⊕⊕ high	Various criteria for abnormal blood urea nitrogen reported ranging from 10.0 mmol/L up to 21.4 mmol/L Significant subgroup effect with increasing level of amino acid intake
	147 per 1000	406 per 1000 (312 to 529)
	Moderate
	53 per 1000	147 per 1000 (113 to 191)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^aWide confidence intervals do not preclude a significant effect. ^bNot reported by a substantial number of studies. ^cStudies had methodological concerns. ^dSignificant and high level of heterogeneity. ^eSingle study at low risk of bias reported a significant effect. ^fWide confidence intervals close to no effect level.

Summary of findings for the main comparison. Higher versus lower amino acid intake in parenteral nutrition for newborn infants

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Table 1. Summary of included studies

Trial	Infants	Higher AA group	Lower AA group	Lipid	Enteral feed
Anderson 1979	Infants at < 37 weeks, AGA	2.5 g/kg/d day 1 to 5	0 g/kg/d day 1 to 5	No lipid. Isocaloric	No enteral feeds
Balasubramanian 2013	Birth weight 900 to 1250 grams	3 g/kg day 1 graded to 4 g/kg day 2	1 g/kg day 1 graded to 4 g/kg day 4	No lipid	Similar early enteral feeds
Black 1981	Infants with respiratory distress	Graded up to 2.8 g/kg/d from day 3 to 4	0 g/kg/d from day 3 to 4	Lipid in amino acid group	Similar delayed enteral feeds
Blanco 2008	Birth weight < 1000 grams	2.0 g/kg day 1 graded to 4.0 g/kg day 3	0.5 g/kg day 2 graded to 3.0 g/kg day 7	Similar lipid from day 1	Enteral feeds unclear
Bulbul 2012	Infants at < 32 weeks' gestation	3 g/kg from day 1	1 g/kg day 1 graded to 3 g/kg day 3	Lipid 3 g/kg day 1 vs 1 g/kg day 1 increasing to 3 g/kg day 3	Similar early enteral feeds
Burattini 2013	Birth weight 500 to 1249 grams	2.5 g/kg day 1 graded to 4.0 g/kg day 4	1.5 g/kg day 1 graded to 2.5 g/kg day 3	Similar lipid from day 5	Similar early enteral feeds
Can 2012	Infants at 27 to 33 weeks' gestation	3.0 g/kg day 1 graded to 4.0 g/kg day 2	1.5 g/kg day 1 graded to 4.0 g/kg day 3	Higher early lipid from day 1 (2 g/kg day 1 and 3 g/kg day 2 vs 1 g/kg day 1 graded to 3 g/kg day 3)	Similar early enteral feeds
Can 2013	Infants at < 32 weeks' gestation	3.0 g/kg day 1 graded to 4.0 g/kg day 2	1.5 g/kg day 1 graded to 4.0 g/kg day 3	Higher early lipid from day 1 (2 g/kg day 1 and 3 g/kg day 2 vs 1 g/kg day 1 graded to 3 g/kg day 3)	Similar early enteral feeds
Clark 2007	Infants at 23 to < 30 weeks' gestation	1.5 g/kg day 2 graded to 3.5 g/kg day 3	1.0 g/kg day 2 graded to 2.5 g/kg day 4	Similar early lipid from day 1	Similar early enteral feeds
Hata 2002	Surgical term infants	3.45 g/kg/d	2.59 g/kg/d vs 1.72 g/kg/d	No lipid	No enteral feeds
Heimler 2010	Infants at < 34 weeks' gestation	1.5 g/kg day 1 graded to 2.5 g/kg day 3	0 g/kg day 1 to 3 graded to 2.5 g/kg day 7	Similar lipid from day 4	No enteral feeds to day 4
Ibrahim 2004	Birth weight 501 to 1250 grams and at 24 to 32 weeks' gestation	3.5 g/kg day 1 to 7	0 g/kg day 1 to 2, 2.0 g/kg day 3 graded to 3.5 g/kg day 7	Higher early lipid from day 1	No enteral feeds to day 7
Kashyap 2007	Birth weight < 1250 grams	18% protein:NPE day 1 graded to 4.0 g/kg/d	12.5% protein:NPE graded to 3.0 g/kg/d	Early lipid from day 1	Similar early enteral feeds
Liu 2014	Birth weight 1000 to 2000 grams	3.0 g/kg day 1 graded to 4.0 g/kg/d	2.0 g/kg day 1 graded to 3.7 g/kg/d 1.0 g/kg day 1 graded to 3.5 g/kg/d	Similar early lipid from day 2	Similar early enteral feeds from day 3
Makay 2007	Infants at ≥ 35 weeks' gestation	1.0 g/kg day 1 graded to 3.0 g/kg day 5	0 g/kg day 1 graded to 3.0 g/kg day 7	Higher lipid from day 2	No enteral feeds
Morgan 2014	Infants at < 29 weeks’ gestation and birth weight < 1200 grams	1.8 g/kg day 1 to 2; 2.9 g/kg day 3 to 4 increased to 3.9 g/kg day 5	1.8 g/kg day 1 to 2; AA 2.4 g/kg day 3 to 4 increased to 2.8 g/kg day 5	Similar early lipid from day 1; higher lipid from day 5 Similar glucose day 1 to 2; higher glucose from day 3	Similar early enteral feeds
Murdoch 1995	Birth weight < 2000 grams	1.0 g/kg day 1 and 1.4 g/kg day 2	0 g/kg day 1 to 2	Higher lipid (no lipid control group)	No enteral feeds
Pappoe 2009	Birth weight 600 to 1200 grams	2.0 g/kg day 1 graded to 3.5 g/kg day 3	1.0 g/kg day 1 graded to 3.5 g/kg day 6	Higher lipid from day 1	Similar early enteral feeds
Pildes 1973	Infants < 1500 grams at 24 to 48 hours' age	Unclear intake (solution 3.4 g/100 mL)	0 g/kg/d	No lipid	Similar enteral feeds
Rivera 1993	Preterm infants with respiratory distress < 24 hours old on mechanical ventilation	1.5 g/kg day 1 to 3	0 g/kg/d	No lipid	No enteral feeds
Scattolin 2013	Birth weight < 1250 grams	2.0 g/kg day 1 graded to 4.0 g/kg day 4	1.5 g/kg day 1 graded to 3.0 g/kg day 4	Lipid intake not reported	Similar early enteral feeds
Tan 2008	Infants at < 33 weeks' gestation	1.0 g/kg day 1 graded to 4.0 g/kg day 7	1.0 g/kg day 1 graded to 3.0 g/kg day 7	Higher lipid from day 1	Similar early enteral feeds
Tang 2009	Birth weight 1000 to 2000 grams	2.4 g/kg day 1 graded to 3.6 g/kg day 2	1.0 g/kg day 1 graded to 3.0 g/kg day 6 vs 0 g/kg day 1 graded to 3.0 g/kg day 9	Similar lipid from day 3	Enteral feeds unclear
te Braake 2005	Birth weight ≤ 1500 grams	2.4 g/kg day 1 to 4	0 g/kg day 1 to 2 graded to 2.4 g/kg day 3 to 4	Similar early lipid from day 2	Similar early enteral feeds
Thureen 2003	Birth weight ≤ 1300 grams	2.56 g/kg day 1 to 2	0.85 g/kg day 1 to 2	Similar early lipid from day 1	No early enteral feeds
Uthaya 2016	Infants at < 31 weeks' gestation	3.6 g/kg/d from day 1	1.7 g/kg/d day 1, 2.1 g/kg/d day 2, maximum 2.7 g/kg/d day 3	Similar early lipid from day 1	Similar early enteral feeds
Vaidya 1995	Birth weight < 1250 grams	0.5 g/kg day 3 graded to 3.0 g/kg day 7	0 g/kg/d	Higher lipid from day 5 (control no lipid)	Early enteral feed
van Goudoever 1995	Birth weight < 2000 grams	1.15 g/kg day 1	0 g/kg/d	No lipid	No enteral feeds
van Lingen 1992	Preterm infants	Average 1.9 g/kg/d	0 g/kg/d	Similar early lipid from day 2	No enteral feeds
Vlaardingerbroek 2013	Birth weight < 1500 grams	3.6 g/kg day 2 to 6	2.4 g/kg day 2 to 6	Similar early lipid from day 1	No enteral feeds
Weiler 2006	Infants at 24 to 32 weeks' gestation	1.0 g/kg day 1 graded to 3.0 g/kg/d	0 g/kg day 1, 1.0 g/kg day 2 graded to 3.0 g/kg/d	Similar lipid from day 3	Factorial trial minimal enteral feeds from 3 days
Wilson 1997	Birth weight < 1200 grams or 1200 to 1499 grams on mechanical ventilation	0.5 g/kg day 1 graded to 3.5 g/kg day 7	0 g/kg day 1 to 2 graded to 2.5 g/kg day 7	Higher early lipid intake from day 1	Higher early enteral intake
Xie 2014	Infants at < 34 weeks' gestation	1.5 g/kg day 1 graded to 3.5 g/kg/d: graded by 1.0 g/kg/d	1.5 g/kg day 1 graded to 3.5 g/kg/d: graded by 0.5 g/kg/d	Similar lipid from day 1	Enteral feeds unclear

Table 1. Summary of included studies

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Comparison 1. Higher versus lower amino acid intake in parenteral nutrition

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality to hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

3 Postnatal growth failure at discharge (weight < 10th centile) Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

4 Postnatal growth failure at discharge (weight 2 SD below mean) Show forest plot	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.66, 1.40]

5 Postnatal growth failure post discharge Show forest plot	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]

6 Days to regain birth weight Show forest plot	13	950	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.73, ‐0.56]

7 Maximal weight loss (grams) Show forest plot	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]

8 Maximal weight loss % Show forest plot	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]

9 Weight gain g/kg/d Show forest plot	7		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 To 1 month age	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]
9.2 To discharge	4	291	Mean Difference (IV, Fixed, 95% CI)	0.76 [‐0.02, 1.54]
10 Linear growth cm/week Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

10.1 To 1 month age	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.26, ‐0.06]
11 Head circumference growth cm/week Show forest plot	7		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

11.1 To 1 month age	4	476	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.06]
11.2 To discharge	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]
12 Weight change z‐score Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

12.1 To 1 month age	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]
12.2 To discharge	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]
12.3 Post discharge	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]
13 Head circumference change z‐score Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

13.1 To 1 month age	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]
13.2 To discharge	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]
13.3 Post discharge	2	201	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐0.14, 0.64]
14 Weight (grams) Show forest plot	12		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

14.1 At 1 month age	4	430	Mean Difference (IV, Fixed, 95% CI)	‐18.45 [‐68.42, 31.52]
14.2 At discharge	10	874	Mean Difference (IV, Fixed, 95% CI)	81.07 [36.59, 125.56]
14.3 Post discharge	2	211	Mean Difference (IV, Fixed, 95% CI)	‐11.07 [‐493.31, 471.18]
15 Length (cm) Show forest plot	8		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

15.1 At 1 month age	3	295	Mean Difference (IV, Fixed, 95% CI)	‐0.41 [‐1.03, 0.20]
15.2 At discharge	6	553	Mean Difference (IV, Fixed, 95% CI)	0.57 [0.17, 0.98]
15.3 Post discharge	1	100	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐1.81, 1.61]
16 Head circumference (cm) Show forest plot	11		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

16.1 At 1 month age	4	430	Mean Difference (IV, Fixed, 95% CI)	0.19 [‐0.13, 0.51]
16.2 At discharge	9	834	Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.14, 0.29]
16.3 Post discharge	2	211	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.52, 0.44]
17 Weight z‐score Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

17.1 Up at 1 month age	1	135	Mean Difference (IV, Fixed, 95% CI)	0.14 [‐0.11, 0.39]
17.2 At discharge	3	352	Mean Difference (IV, Fixed, 95% CI)	0.16 [‐0.02, 0.33]
18 Length z‐score Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

18.1 At discharge	2	228	Mean Difference (IV, Fixed, 95% CI)	0.12 [‐0.14, 0.38]
19 Head circumference z‐score Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

19.1 At 1 month age	1	135	Mean Difference (IV, Fixed, 95% CI)	0.30 [0.01, 0.59]
19.2 At discharge	3	354	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.18, 0.26]
19.3 Post discharge	1	100	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.50, 0.48]
20 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

21 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

22 Necrotising enterocolitis Show forest plot	14	1301	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.68, 1.47]

23 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

24 Patent ductus arteriosus Show forest plot	7	607	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.67, 1.02]

25 Intraventricular haemorrhage Show forest plot	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]

26 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

27 Periventricular leukomalacia Show forest plot	7	720	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.24, 1.25]

28 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

29 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

30 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

31 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

32 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

33 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

34 Bayley MDI at ≥ 18 months Show forest plot	2	105	Mean Difference (IV, Fixed, 95% CI)	‐4.18 [‐8.53, 0.17]

35 Bayley III score at ≥ 18 months Show forest plot	1	100	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐2.52, 8.52]

36 Bayley PDI at ≥ 18 months Show forest plot	1	32	Mean Difference (IV, Fixed, 95% CI)	3.00 [‐6.41, 12.41]

37 Autism Show forest plot	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 14.64]

38 Nitrogen balance Show forest plot	6	153	Mean Difference (IV, Fixed, 95% CI)	505.20 [492.01, 518.39]

38.1 AA 1.0 g/kg increase per day vs 0.5 g/kg increase per day	1	37	Mean Difference (IV, Fixed, 95% CI)	31.77 [‐61.98, 125.51]
38.2 AA 1.15 g/kg/day vs 0 g/kg/day	1	15	Mean Difference (IV, Fixed, 95% CI)	120.00 [21.10, 218.90]
38.3 AA 1.5 g/kg/day vs 0 g/kg/day	1	23	Mean Difference (IV, Fixed, 95% CI)	223.0 [182.18, 263.82]
38.4 AA 2.0‐2.5 g/kg/day vs 0‐0.4 g/kg/day	2	49	Mean Difference (IV, Fixed, 95% CI)	280.75 [234.74, 326.76]
38.5 AA 3.5 g/kg/day vs 0 g/kg/day	1	29	Mean Difference (IV, Fixed, 95% CI)	587.9 [572.92, 602.88]
39 Protein balance Show forest plot	3	52	Mean Difference (IV, Fixed, 95% CI)	1.57 [1.47, 1.66]

39.1 AA 1.5 g/kg/day vs 0 g/kg/day	1	12	Mean Difference (IV, Fixed, 95% CI)	1.1 [0.16, 2.04]
39.2 AA 2.3 g/kg/day vs 0 g/kg/day	1	18	Mean Difference (IV, Fixed, 95% CI)	2.0 [1.82, 2.18]
39.3 AA 3 g/kg/day vs 1 g/kg/day	1	22	Mean Difference (IV, Fixed, 95% CI)	1.42 [1.31, 1.53]
40 Abnormal serum ammonia Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

40.1 Ammonia > 69 μmol/L	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	13.42 [0.79, 228.24]
40.2 Ammonia > 100 μmol/L	2	105	Risk Ratio (M‐H, Fixed, 95% CI)	9.29 [0.52, 165.45]
40.3 Ammonia > 122 μmol/L	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
41 Abnormal blood urea nitrogen (various criteria) Show forest plot	7	688	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.13, 3.61]

41.1 AA started 0.5 g/kg/day and graded to 3.0 g/kg/day vs 0 g/kg/day: high BUN criteria not reported	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	10.74 [1.45, 79.59]
41.2 AA started 2 g/kg/day and graded to 3.5 g/kg/day vs started 1.0 g/kg/day and graded to 3.5 g/kg/day: BUN > 14.3 mmol/L	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	2.48 [0.28, 21.93]
41.3 AA started 1.5 g/kg/day and graded to 3.5 g/kg/day vs started 1.0 g/kg/day and graded to 2.5 g/kg/day: BUN > 17.85 mmol/L	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	6.35 [0.34, 120.45]
41.4 AA started 2 g/kg/day and graded to 4.0 g/kg/day vs started 0.5 g/kg/day and graded to 3.0 g/kg/day: BUN > 21.4 mmol/L	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	19.61 [1.19, 322.72]
41.5 AA started 2.5 g/kg/day and graded to 4.0 g/kg/day vs started 1.5 g/kg/day and graded to 2.5 g/kg/day: BUN > 11.6 mmol/L	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	2.44 [1.47, 4.05]
41.6 AA started 3.6 g/kg/day vs started 1.7 g/kg/day amino acids and graded to 2.7 g/kg/day: BUN > 10 mmol/L	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	2.73 [1.64, 4.54]
41.7 AA 3.6 g/kg/day vs 2.4 g/kg/day: BUN > 10 mmol/L	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	2.09 [1.43, 3.04]
42 Maximum blood urea nitrogen mmol/L Show forest plot	2	159	Mean Difference (IV, Fixed, 95% CI)	4.48 [3.43, 5.53]

43 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]

44 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

45 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

46 Metabolic acidosis Show forest plot	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

47 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

48 Hyperkalaemia Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.16, 2.37]

49 Discontinued PN owing to biochemical intolerance Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	13.42 [0.79, 228.24]

Comparison 1. Higher versus lower amino acid intake in parenteral nutrition

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Comparison 2. Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	6	433	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.45, 1.36]

1.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	1.65 [0.16, 16.85]
1.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	3	263	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.35, 1.76]
1.3 Very high amino acid intake (> 3 g/kg/day)	2	128	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.30, 1.57]
2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

2.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.18, 1.29]
2.2 Very high amino acid intake (> 3 g/kg/day)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	7.0 [0.90, 54.60]
3 Postnatal growth failure at discharge Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

3.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.62, 1.46]
3.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	161	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.48, 0.94]
4 Postnatal growth failure post discharge Show forest plot	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]

4.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]
5 Days to regain birth weight Show forest plot	6	303	Mean Difference (IV, Fixed, 95% CI)	0.43 [‐0.51, 1.37]

5.1 Very low amino acid intake (≤ 1 g/kg/day)	1	27	Mean Difference (IV, Fixed, 95% CI)	‐1.45 [‐4.45, 1.56]
5.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	59	Mean Difference (IV, Fixed, 95% CI)	‐1.40 [‐3.66, 0.85]
5.3 High amino acid intake (> 2 to ≤ 3 g/kg/day)	3	217	Mean Difference (IV, Fixed, 95% CI)	1.13 [0.02, 2.23]
6 Maximal weight loss (grams) Show forest plot	1	50	Mean Difference (IV, Fixed, 95% CI)	22.60 [‐7.25, 52.45]

6.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	50	Mean Difference (IV, Fixed, 95% CI)	22.60 [‐7.25, 52.45]
7 Maximal weight loss % Show forest plot	2	59	Mean Difference (IV, Fixed, 95% CI)	‐2.73 [‐5.71, 0.25]

7.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	59	Mean Difference (IV, Fixed, 95% CI)	‐2.73 [‐5.71, 0.25]
8 Weight gain g/kg/day to 1 month age Show forest plot	2	219	Mean Difference (IV, Fixed, 95% CI)	‐3.17 [‐4.49, ‐1.84]

8.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	123	Mean Difference (IV, Fixed, 95% CI)	‐4.48 [‐6.17, ‐2.79]
8.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	‐1.10 [‐3.22, 1.02]
9 Weight gain g/kg/day to discharge Show forest plot	2	140	Mean Difference (IV, Fixed, 95% CI)	1.05 [‐0.55, 2.66]

9.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Mean Difference (IV, Fixed, 95% CI)	0.40 [‐1.69, 2.49]
9.2 Very high amino acid intake (> 3 g/kg/day)	1	98	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐0.51, 4.51]
10 Linear growth cm/week to 1 month age Show forest plot	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]

10.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]
11 Head circumference growth cm/week to 1 month age Show forest plot	2	219	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.21, ‐0.04]

11.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐0.51, ‐0.24]
11.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.09, 0.13]
12 Head circumference growth cm/week to discharge Show forest plot	1	96	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.03, 0.09]

12.1 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.03, 0.09]
13 Weight change z‐score to 1 month age Show forest plot	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]

13.1 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]
14 Weight change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]

14.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Mean Difference (IV, Fixed, 95% CI)	‐0.22 [‐0.70, 0.26]
14.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	0.27 [‐0.23, 0.77]
15 Weight change z‐score post discharge Show forest plot	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]

15.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐0.75, 0.41]
15.2 Very high amino acid intake (> 3 g/kg/day)	1	90	Mean Difference (IV, Fixed, 95% CI)	0.38 [‐0.15, 0.91]
16 Head circumference change z‐score to 1 month age Show forest plot	1	96	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.36, 0.36]

16.1 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.36, 0.36]
17 Head circumference change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]

17.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.66, 0.36]
17.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Mean Difference (IV, Fixed, 95% CI)	0.4 [‐0.02, 0.82]
18 Head circumference change z‐score post discharge Show forest plot	2	201	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐0.14, 0.64]

18.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.46, 0.52]
18.2 Very high amino acid intake (> 3 g/kg/day)	1	90	Mean Difference (IV, Fixed, 95% CI)	0.61 [‐0.02, 1.23]
19 Days to full enteral feeds Show forest plot	4	196	Mean Difference (IV, Fixed, 95% CI)	‐0.22 [‐1.60, 1.17]

19.1 Very low amino acid intake (≤ 1 g/kg/day)	1	27	Mean Difference (IV, Fixed, 95% CI)	‐0.91 [‐9.80, 7.98]
19.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	3	169	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐1.60, 1.20]
20 Late‐onset sepsis Show forest plot	5	319	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.65, 1.38]

20.1 Very low amino acid intake (≤ 1 g/kg/day)	1	27	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.40, 2.88]
20.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	167	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.35, 2.00]
20.3 Very high amino acid intake (> 3 g/kg/day)	2	125	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.61, 1.52]
21 Necrotising enterocolitis Show forest plot	5	340	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.45, 2.03]

21.1 Very low amino acid intake (≤ 1 g/kg/day)	1	27	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
21.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	3	217	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.55, 2.92]
21.3 Very high amino acid intake (> 3 g/kg/day)	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.26 [0.03, 2.25]
22 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	4	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.86, 2.02]

22.1 Very low amino acid intake (≤ 1 g/kg/day)	1	27	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.34, 3.44]
22.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 15.12]
22.3 Very high amino acid intake (> 3 g/kg/day)	2	125	Risk Ratio (M‐H, Fixed, 95% CI)	1.39 [0.87, 2.21]
23 Patent ductus arteriosus Show forest plot	4	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.50, 1.07]

23.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.63, 1.74]
23.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	173	Risk Ratio (M‐H, Fixed, 95% CI)	0.42 [0.20, 0.89]
23.3 Very high amino acid intake (> 3 g/kg/day)	1	29	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.50, 2.28]
24 Intraventricular haemorrhage Show forest plot	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.41, 3.91]

24.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.41, 3.91]
25 Severe intraventricular haemorrhage Show forest plot	5	261	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [0.66, 3.17]

25.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	3.30 [0.40, 27.13]
25.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	94	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.19, 20.67]
25.3 Very high amino acid intake (> 3 g/kg/day)	2	125	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.42, 2.69]
26 Periventricular leukomalacia Show forest plot	2	146	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.81]

26.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.81]
26.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
27 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

27.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.10, 2.96]
27.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	198	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.14, 0.95]
27.3 Very high amino acid intake (> 3 g/kg/day)	1	29	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.14, 3.66]
28 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	4	265	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.20, 1.11]

28.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.10, 2.96]
28.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	125	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.06, 0.85]
28.3 Very high amino acid intake (> 3 g/kg/day)	1	98	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 101.53]
29 Cerebral palsy Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.61, 41.11]

29.1 Very high amino acid intake (> 3 g/kg/day)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.61, 41.11]
30 Developmental delay at ≥ 18 months Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.35, 3.11]

30.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.24, 2.98]
30.2 Very high amino acid intake (> 3 g/kg/day)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.19, 21.28]
31 Blindness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

31.1 Very high amino acid intake (> 3 g/kg/day)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
32 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

32.1 Very high amino acid intake (> 3 g/kg/day)	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
33 Abnormal serum ammonia (> 100 μmol/L) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

33.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	44	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
34 Abnormal blood urea nitrogen (various criteria) Show forest plot	2	138	Risk Ratio (M‐H, Fixed, 95% CI)	2.11 [1.44, 3.08]

34.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	2.48 [0.28, 21.93]
34.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	2.09 [1.43, 3.04]
35 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.85, 2.53]

35.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.85, 2.53]
36 Hyperglycaemia treated with insulin Show forest plot	2	138	Risk Ratio (M‐H, Fixed, 95% CI)	1.84 [0.97, 3.49]

36.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	42	Risk Ratio (M‐H, Fixed, 95% CI)	4.96 [1.26, 19.47]
36.2 Very high amino acid intake (> 3 g/kg/day)	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.54, 2.45]
37 Hypoglycaemia Show forest plot	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.68 [0.83, 3.41]

37.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.68 [0.83, 3.41]
38 Metabolic acidosis Show forest plot	1	15	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

38.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	15	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Higher versus lower amino acid intake at commencement of parenteral nutrition: subgrouped by commencement intake

Ir a la tabla de la revisión

Comparison 3. Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	2	292	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.57, 1.55]

1.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	292	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.57, 1.55]
2 Head circumference growth cm/week to 1 month Show forest plot	1	135	Mean Difference (IV, Fixed, 95% CI)	0.13 [0.05, 0.20]

2.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	135	Mean Difference (IV, Fixed, 95% CI)	0.13 [0.05, 0.20]
3 Head circumference change z‐score to 1 month Show forest plot	1	135	Mean Difference (IV, Fixed, 95% CI)	0.37 [0.15, 0.59]

3.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	135	Mean Difference (IV, Fixed, 95% CI)	0.37 [0.15, 0.59]
4 Days to regain birth weight Show forest plot	1	114	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐5.88, ‐1.32]

4.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	114	Mean Difference (IV, Fixed, 95% CI)	‐3.60 [‐5.88, ‐1.32]
5 Days to full enteral feeds Show forest plot	1	114	Mean Difference (IV, Fixed, 95% CI)	4.0 [1.01, 6.99]

5.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	114	Mean Difference (IV, Fixed, 95% CI)	4.0 [1.01, 6.99]
6 Late‐onset sepsis Show forest plot	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.63, 1.41]

6.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.63, 1.41]
7 Necrotising enterocolitis Show forest plot	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.37, 1.59]

7.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.37, 1.59]
8 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.92, 1.31]

8.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.92, 1.31]
9 Patent ductus arteriosus Show forest plot	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.66, 1.56]

9.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.66, 1.56]
10 Severe intraventricular haemorrhage Show forest plot	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.51, 2.63]

10.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.51, 2.63]
11 Periventricular leukomalacia Show forest plot	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [0.39, 10.70]

11.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [0.39, 10.70]
12 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	2.71 [0.75, 9.75]

12.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	2.71 [0.75, 9.75]
13 Hyperglycaemia treated with insulin Show forest plot	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	1.69 [1.12, 2.53]

13.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	1.69 [1.12, 2.53]
14 Cholestasis Show forest plot	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.76, 1.94]

14.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	241	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.76, 1.94]

Comparison 3. Higher versus lower amino acid intake at maximal intake of parenteral nutrition: subgrouped by maximal intake

Ir a la tabla de la revisión

Comparison 4. Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality to hospital discharge Show forest plot	5	567	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.66, 1.42]

1.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.72, 1.81]
1.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	183	Risk Ratio (M‐H, Fixed, 95% CI)	1.61 [0.56, 4.57]
1.3 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	131	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.24, 2.98]
1.4 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.45 [0.17, 1.25]
2 Days to regain birth weight Show forest plot	5	496	Mean Difference (IV, Fixed, 95% CI)	‐1.86 [‐2.79, ‐0.93]

2.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐5.03, 3.03]
2.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	115	Mean Difference (IV, Fixed, 95% CI)	‐1.33 [‐3.74, 1.08]
2.3 High amino acid intake (> 2 to ≤ 3 g/kg/day)	3	296	Mean Difference (IV, Fixed, 95% CI)	‐2.02 [‐3.06, ‐0.97]
3 Maximal weight loss (grams) Show forest plot	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]

3.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]
4 Maximal weight loss % Show forest plot	2	229	Mean Difference (IV, Fixed, 95% CI)	0.22 [‐1.20, 1.64]

4.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	115	Mean Difference (IV, Fixed, 95% CI)	0.51 [‐1.66, 2.68]
4.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐1.87, 1.87]
5 Weight gain g/kg/day up to 1 month age Show forest plot	2	154	Mean Difference (IV, Fixed, 95% CI)	1.48 [‐0.29, 3.25]

5.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	154	Mean Difference (IV, Fixed, 95% CI)	1.48 [‐0.29, 3.25]
6 Weight gain g/kg/day to discharge Show forest plot	1	114	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.34, 1.54]

6.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.34, 1.54]
7 Linear growth cm/week up to 1 month age Show forest plot	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]

7.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
8 Head circumference growth cm/week up to 1 month age Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.12, 0.12]
9 Head circumference growth cm/week to discharge Show forest plot	2	182	Mean Difference (IV, Fixed, 95% CI)	0.11 [0.07, 0.15]

9.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	182	Mean Difference (IV, Fixed, 95% CI)	0.11 [0.07, 0.15]
10 Days to full enteral feeds Show forest plot	5	431	Mean Difference (IV, Fixed, 95% CI)	‐1.08 [‐2.42, 0.25]

10.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	147	Mean Difference (IV, Fixed, 95% CI)	2.47 [‐1.73, 6.68]
10.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	158	Mean Difference (IV, Fixed, 95% CI)	‐3.32 [‐5.39, ‐1.25]
10.3 Very high amino acid intake (> 3 g/kg/day)	1	126	Mean Difference (IV, Fixed, 95% CI)	0.09 [‐1.83, 2.01]
11 Late‐onset sepsis Show forest plot	8	772	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.72, 1.29]

11.1 Very low amino acid intake (≤ 1 g/kg/day)	2	106	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.27, 1.95]
11.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	3	288	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.67, 1.80]
11.3 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	210	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.56, 2.69]
11.4 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.52, 1.30]
12 Necrotising enterocolitis Show forest plot	6	683	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.63, 2.07]

12.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	3	288	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [0.72, 3.87]
12.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.19, 3.47]
12.3 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.24, 2.16]
13 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	4	376	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.55, 1.19]

13.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	166	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.66, 1.69]
13.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	210	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.29, 1.08]
14 Patent ductus arteriosus Show forest plot	2	236	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.60, 1.10]

14.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.40, 1.07]
14.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.65, 1.42]
15 Intraventricular haemorrhage Show forest plot	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.70, 1.70]

15.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.64, 1.73]
15.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.47, 3.13]
16 Severe intraventricular haemorrhage Show forest plot	4	402	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.46, 2.02]

16.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	3	288	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.47, 2.29]
16.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.05, 5.55]
17 Periventricular leukomalacia Show forest plot	4	447	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.10, 1.00]

17.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	237	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.03, 0.79]
17.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	210	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.20, 9.33]
18 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	3	280	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.49, 3.09]

18.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	166	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.49, 3.09]
18.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
19 Cerebral palsy Show forest plot	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.35, 25.87]

19.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.35, 25.87]
20 Developmental delay at ≥ 18 months Show forest plot	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]

20.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]
21 Blindness Show forest plot	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

21.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
22 Abnormal serum ammonia Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

22.1 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
23 Abnormal blood urea nitrogen (various criteria) Show forest plot	5	550	Risk Ratio (M‐H, Fixed, 95% CI)	3.19 [2.24, 4.53]

23.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	10.74 [1.45, 79.59]
23.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	2	183	Risk Ratio (M‐H, Fixed, 95% CI)	12.29 [1.66, 90.79]
23.3 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	2.44 [1.47, 4.05]
23.4 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	2.73 [1.64, 4.54]
24 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	4	463	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.36, 0.82]

24.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.95 [0.18, 20.74]
24.2 High amino acid intake (> 2 to ≤ 3 g/kg/day)	2	210	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.30, 0.87]
24.3 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.26, 1.06]
25 Hyperglycaemia treated with insulin Show forest plot	2	282	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.35, 1.08]

25.1 High amino acid intake (> 2 to ≤ 3 g/kg/day)	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.04, 3.22]
25.2 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.37, 1.16]
26 Hypoglycaemia Show forest plot	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.70, 1.50]

26.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.35, 4.24]
26.2 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.67, 1.49]
27 Metabolic acidosis Show forest plot	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

27.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	8.80 [0.49, 158.47]
27.2 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.71, 3.72]
28 Cholestasis Show forest plot	3	375	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.71, 2.50]

28.1 Very low amino acid intake (≤ 1 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	12.70 [0.74, 218.66]
28.2 Low amino acid intake (> 1 to ≤ 2 g/kg/day)	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.50, 4.18]
28.3 Very high amino acid intake (> 3 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	0.7 [0.28, 1.75]

Comparison 4. Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by commencement intake

Ir a la tabla de la revisión

Comparison 5. Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	5	567	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.66, 1.42]

2 Days to regain birth weight Show forest plot	5	496	Mean Difference (IV, Fixed, 95% CI)	‐1.86 [‐2.79, ‐0.93]

2.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐5.03, 3.03]
2.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	4	411	Mean Difference (IV, Fixed, 95% CI)	‐1.91 [‐2.87, ‐0.95]
3 Maximal weight loss (grams) Show forest plot	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]

3.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]
4 Maximal weight loss % Show forest plot	2	229	Mean Difference (IV, Fixed, 95% CI)	0.22 [‐1.20, 1.64]

4.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	229	Mean Difference (IV, Fixed, 95% CI)	0.22 [‐1.20, 1.64]
5 Weight gain g/kg/day up to 1 month Show forest plot	2	154	Mean Difference (IV, Fixed, 95% CI)	1.48 [‐0.29, 3.25]

5.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	154	Mean Difference (IV, Fixed, 95% CI)	1.48 [‐0.29, 3.25]
6 Weight gain g/kg/day to discharge Show forest plot	1	114	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.34, 1.54]

6.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	114	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.34, 1.54]
7 Linear growth cm/week up to 1 month Show forest plot	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]

7.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
8 Head circumference growth cm/week up to 1 month Show forest plot	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.12, 0.12]

8.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.12, 0.12]
9 Head circumference growth cm/week to discharge Show forest plot	2	182	Mean Difference (IV, Fixed, 95% CI)	0.11 [0.07, 0.15]

9.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	182	Mean Difference (IV, Fixed, 95% CI)	0.11 [0.07, 0.15]
10 Days to full enteral feeds Show forest plot	5	431	Mean Difference (IV, Fixed, 95% CI)	‐1.08 [‐2.42, 0.25]

10.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	5	431	Mean Difference (IV, Fixed, 95% CI)	‐1.08 [‐2.42, 0.25]
11 Late‐onset sepsis Show forest plot	8	772	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.72, 1.29]

11.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	2	106	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.27, 1.95]
11.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	6	666	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.73, 1.35]
12 Necrotising enterocolitis Show forest plot	6	683	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.63, 2.07]

12.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	6	683	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.63, 2.07]
13 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	4	376	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.55, 1.19]

13.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	4	376	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.55, 1.19]
14 Patent ductus arteriosus Show forest plot	2	236	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.60, 1.10]

14.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	236	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.60, 1.10]
15 Intraventricular haemorrhage Show forest plot	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.70, 1.70]

15.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.70, 1.70]
16 Severe intraventricular haemorrhage Show forest plot	4	402	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.46, 2.02]

16.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	4	402	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.46, 2.02]
17 Periventricular leukomalacia Show forest plot	4	447	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.10, 1.00]

17.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	4	447	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.10, 1.00]
18 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	3	280	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.49, 3.09]

18.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	3	280	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.49, 3.09]
19 Cerebral palsy Show forest plot	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.35, 25.87]

19.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.35, 25.87]
20 Developmental delay at ≥ 18 months Show forest plot	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]

20.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]
21 Blindness Show forest plot	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

21.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	32	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
22 Abnormal serum ammonia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

22.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
23 Abnormal blood urea nitrogen (various criteria) Show forest plot	5	550	Risk Ratio (M‐H, Fixed, 95% CI)	3.19 [2.24, 4.53]

23.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	10.74 [1.45, 79.59]
23.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	4	465	Risk Ratio (M‐H, Fixed, 95% CI)	2.93 [2.05, 4.18]
24 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	4	463	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.36, 0.82]

24.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.95 [0.18, 20.74]
24.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	3	378	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.34, 0.79]
25 Hyperglycaemia treated with insulin Show forest plot	2	282	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.35, 1.08]

25.1 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	282	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.35, 1.08]
26 Hypoglycaemia Show forest plot	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.70, 1.50]

26.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.35, 4.24]
26.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.67, 1.49]
27 Metabolic acidosis Show forest plot	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

27.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	8.80 [0.49, 158.47]
27.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.71, 3.72]
28 Cholestasis Show forest plot	3	375	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.71, 2.50]

28.1 Low amino acid intake (> 2 to ≤ 3 g/kg/day)	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	12.70 [0.74, 218.66]
28.2 High amino acid intake (> 3 to ≤ 4 g/kg/day)	2	290	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.48, 1.90]

Comparison 5. Higher versus lower amino acid intake at commencement and maximal intake of parenteral nutrition: subgrouped by maximal intake

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Comparison 6. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality to hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

1.1 Increase amino acids and provide isocaloric non‐protein intake	7	828	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.51, 1.20]
1.2 Increase amino acids and non‐protein caloric intake	7	579	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.71, 1.39]
2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

2.1 Increase amino acids and provide isocaloric non‐protein intake	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]
3 Postnatal growth failure at discharge Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

3.1 Increase amino acids and provide isocaloric non‐protein intake	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.44, 1.30]
3.2 Increase amino acids and non‐protein caloric intake	2	92	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.55, 0.98]
4 Days to regain birth weight Show forest plot	13	950	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.73, ‐0.56]

4.1 Increase amino acids and provide isocaloric non‐protein intake	8	615	Mean Difference (IV, Fixed, 95% CI)	‐1.06 [‐1.77, ‐0.34]
4.2 Increase amino acids and non‐protein caloric intake	5	335	Mean Difference (IV, Fixed, 95% CI)	‐1.32 [‐2.33, ‐0.31]
5 Maximal weight loss (grams) Show forest plot	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]

5.1 Increase amino acids and provide isocaloric non‐protein intake	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]
5.2 Increase amino acids and non‐protein caloric intake	1	50	Mean Difference (IV, Fixed, 95% CI)	22.60 [‐7.25, 52.45]
6 Maximal weight loss % Show forest plot	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]

6.1 Increase amino acids and provide isocaloric non‐protein intake	3	246	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐1.13, 1.64]
6.2 Increase amino acids and non‐protein caloric intake	1	42	Mean Difference (IV, Fixed, 95% CI)	‐3.80 [‐7.20, ‐0.40]
7 Weight gain g/kg/day up to 1 month Show forest plot	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]

7.1 Increase amino acids and provide isocaloric non‐protein intake	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]
8 Weight gain g/kg/day to discharge Show forest plot	4	291	Mean Difference (IV, Fixed, 95% CI)	0.76 [‐0.02, 1.54]

8.1 Increase amino acids and provide isocaloric non‐protein nutrition	3	249	Mean Difference (IV, Fixed, 95% CI)	0.81 [‐0.03, 1.66]
8.2 Increase amino acids and non‐protein caloric intake	1	42	Mean Difference (IV, Fixed, 95% CI)	0.40 [‐1.69, 2.49]
9 Linear growth cm/week up to 1 month Show forest plot	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]

9.1 Increase amino acids and provide isocaloric non‐protein intake	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
10 Linear growth cm/week to discharge Show forest plot	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]

10.1 Increase amino acids and provide isocaloric non‐protein intake	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]
11 Head circumference growth cm/week up to 1 month Show forest plot	3	380	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.05, 0.07]

11.1 Increase amino acids and provide isocaloric non‐protein intake	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.25, ‐0.07]
11.2 Increase amino acids and non‐protein caloric intake	1	135	Mean Difference (IV, Fixed, 95% CI)	0.13 [0.05, 0.20]
12 Head circumference growth cm/week to discharge Show forest plot	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]

12.1 Increase amino acids and provide isocaloric non‐protein intake	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]
13 Weight change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]

13.1 Increase amino acids and provide isocaloric non‐protein intake	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]
14 Head circumference change z‐score to 1 month Show forest plot	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]

14.1 Increase amino acids and provide isocaloric non‐protein intake	1	96	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.36, 0.36]
14.2 Increase amino acids and non‐protein caloric intake	1	135	Mean Difference (IV, Fixed, 95% CI)	0.37 [0.15, 0.59]
15 Head circumference change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]

15.1 Increase amino acids and provide isocaloric non‐protein intake	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]
16 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

16.1 Increase amino acids and provide isocaloric non‐protein intake	7	495	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐2.14, 0.35]
16.2 Increase amino acids and non‐protein caloric intake	4	283	Mean Difference (IV, Fixed, 95% CI)	0.56 [‐0.71, 1.83]
17 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

17.1 Increase amino acids and provide isocaloric non‐protein intake	10	949	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.77, 1.27]
17.2 Increase amino acids and non‐protein caloric intake	5	306	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.64, 1.27]
18 Necrotising enterocolitis Show forest plot	14	1301	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.68, 1.47]

18.1 Increase amino acids and provide isocaloric non‐protein intake	10	966	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.69, 1.79]
18.2 Increase amino acids and non‐protein caloric intake	4	335	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.41, 1.56]
19 Chronic lung disease ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

19.1 Increase amino acids and provide isocaloric non‐protein intake	6	499	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.70, 1.31]
19.2 Increase amino acids and non‐protein caloric intake	4	320	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.93, 1.31]
20 Intraventricular haemorrhage Show forest plot	4	370	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.73, 1.59]

20.1 Increase amino acids and provide isocaloric non‐protein intake	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]
20.2 Increase amino acids and non‐protein caloric intake	1	29	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.29, 2.56]
21 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

21.1 Increase amino acids and provide isocaloric non‐protein intake	6	527	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.56, 1.78]
21.2 Increase amino acids and non‐protein caloric intake	5	377	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.70, 2.92]
22 Periventricular leukomalacia Show forest plot	7	720	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.24, 1.25]

22.1 Increase amino acids and provide isocaloric non‐protein intake	5	543	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.10, 1.00]
22.2 Increase amino acids and non‐protein caloric intake	2	177	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.33, 5.11]
23 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

23.1 Increase amino acids and provide isocaloric non‐protein intake	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.27, 9.10]
23.2 Increase amino acids and non‐protein caloric intake	3	146	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.13, 0.77]
24 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

24.1 Increase amino acids and provide isocaloric non‐protein intake	4	378	Risk Ratio (M‐H, Fixed, 95% CI)	1.50 [0.63, 3.55]
24.2 Increase amino acids and non‐protein caloric intake	4	294	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.36, 1.46]
25 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

25.1 Increase amino acids and provide isocaloric non‐protein intake	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]
26 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

26.1 Increase amino acids and provide isocaloric non‐protein calorie nutrition	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]
27 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

27.1 Increase amino acids and provide isocaloric non‐protein intake	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
28 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

28.1 Increase amino acids and provide isocaloric non‐protein intake	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
29 Abnormal serum ammonia Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

29.1 Increase amino acids and provide isocaloric non‐protein intake	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
30 Abnormal blood urea nitrogen (various criteria) Show forest plot	7	688	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.13, 3.61]

30.1 Increase amino acids and provide isocaloric non‐protein intake	5	561	Risk Ratio (M‐H, Fixed, 95% CI)	2.61 [2.00, 3.41]
30.2 Increase amino acids and non‐protein calorie nutrition	2	127	Risk Ratio (M‐H, Fixed, 95% CI)	6.45 [1.55, 26.84]
31 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]

31.1 Increase amino acids and provide isocaloric non‐protein intake	3	378	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.34, 0.79]
31.2 Increase amino acids and non‐protein calorie nutrition	2	127	Risk Ratio (M‐H, Fixed, 95% CI)	1.51 [0.88, 2.62]
32 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

32.1 Increase amino acids and provide isocaloric non‐protein intake	3	378	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.49, 1.19]
32.2 Increase amino acids and non‐protein calorie nutrition	2	156	Risk Ratio (M‐H, Fixed, 95% CI)	2.00 [1.35, 2.98]
33 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

33.1 Increase amino acids and provide isocaloric non‐protein intake	2	291	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.82, 1.64]
33.2 Increase amino acids and non‐protein calorie nutrition	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.35, 4.24]
34 Metabolic acidosis Show forest plot	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

34.1 Increase amino acids and provide isocaloric non‐protein intake	3	220	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.71, 3.72]
34.2 Increase amino acids and non‐protein calorie nutrition	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	8.80 [0.49, 158.47]
35 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

35.1 Increase amino acids and provide isocaloric non‐protein intake	2	290	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.48, 1.90]
35.2 Increase amino acids and non‐protein calorie nutrition	3	326	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.92, 2.28]

Comparison 6. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to management of caloric balance

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Comparison 7. Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

3 Postnatal growth failure Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 At latest time measured to discharge	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]
3.2 Post discharge	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]
4 Days to regain birth weight Show forest plot	10	800	Mean Difference (IV, Fixed, 95% CI)	‐0.78 [‐1.46, ‐0.11]

5 Maximal weight loss (grams) Show forest plot	2	139	Mean Difference (IV, Fixed, 95% CI)	‐20.37 [‐32.68, ‐8.05]

6 Maximal weight loss % Show forest plot	3	271	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐1.69, 0.93]

7 Weight gain g/kg/day Show forest plot	6		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Up to 1 month age	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]
7.2 At latest time measured to discharge	3	254	Mean Difference (IV, Fixed, 95% CI)	0.72 [‐0.09, 1.52]
8 Linear growth cm/week Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

8.1 Up to 1 month age	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.26, ‐0.06]
9 Head circumference growth cm/week Show forest plot	5	658	Mean Difference (IV, Fixed, 95% CI)	0.06 [0.03, 0.09]

9.1 Up to 1 month age	4	476	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.06]
9.2 At latest time measured to discharge	2	182	Mean Difference (IV, Fixed, 95% CI)	0.08 [0.05, 0.12]
10 Weight change z‐score Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

10.1 Up to 1 month age	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]
10.2 At latest time measured to discharge	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]
10.3 Post discharge	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]
11 Head circumference change z‐score Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

11.1 Up to 1 month age	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]
11.2 At latest time measured to discharge	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]
11.3 Post discharge	2	201	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐0.14, 0.64]
12 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

13 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

14 Necrotising enterocolitis Show forest plot	14	1301	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.68, 1.47]

15 Chronic lung disease ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

16 Intraventricular haemorrhage Show forest plot	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]

17 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

18 Periventricular leukomalacia Show forest plot	6	624	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.20, 1.17]

19 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

20 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

21 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

22 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

22.1 MDI < 70	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.35, 3.11]
22.2 Severe mental retardation	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]
23 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

24 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

25 Abnormal serum ammonia > 122 μmol/L Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

26 Abnormal blood urea nitrogen > 21.4 mmol/L Show forest plot	7	688	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.13, 3.61]

27 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	4	409	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.45, 0.96]

28 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

29 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

30 Metabolic acidosis Show forest plot	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

31 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

Comparison 7. Higher versus lower amino acid intake in parenteral nutrition: very preterm or very low birth weight infants

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Comparison 8. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

1.1 Commenced < 24 hours	12	1200	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.60, 1.13]
1.2 Commenced ≥ 24 to < 48 hours	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.81 [0.17, 19.47]
1.3 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.72, 1.81]
2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

2.1 Commenced < 24 hours	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]
3 Postnatal growth failure at discharge Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

3.1 Commenced < 24 hours	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]
4 Days to regain birth weight Show forest plot	13	950	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.73, ‐0.56]

4.1 Commenced < 24 hours	12	865	Mean Difference (IV, Fixed, 95% CI)	‐1.15 [‐1.74, ‐0.56]
4.2 Commenced ≥ 48 to < 72 hours	1	85	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐5.03, 3.03]
5 Maximal weight loss (grams) Show forest plot	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]

5.1 Commenced < 24 hours	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]
6 Maximal weight loss % Show forest plot	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]

6.1 Commenced < 24 hours	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]
7 Weight gain g/kg/day up to 1 month Show forest plot	1	122	Mean Difference (IV, Fixed, 95% CI)	1.5 [‐0.27, 3.27]

7.1 Commenced ≥ 24 to < 48 hours	1	122	Mean Difference (IV, Fixed, 95% CI)	1.5 [‐0.27, 3.27]
8 Weight gain g/kg/day to discharge Show forest plot	6	446	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.87, 0.54]

8.1 Commenced < 24 hours	5	348	Mean Difference (IV, Fixed, 95% CI)	‐0.35 [‐1.09, 0.39]
8.2 Commenced ≥ 24 to < 48 hours	1	98	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐0.51, 4.51]
9 Linear growth cm/week up to 1 month Show forest plot	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.26, ‐0.06]

9.1 Commenced < 24 hours	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]
9.2 Commenced ≥ 24 to < 48 hours	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
10 Head circumference growth cm/week up to 1 month age Show forest plot	4	476	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.06]

10.1 Commenced < 24 hours	2	258	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.06, 0.08]
10.2 Commenced ≥ 24 to < 48 hours	2	218	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.07, 0.09]
11 Head circumference growth cm/week to discharge Show forest plot	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]

11.1 Commenced < 24 hours	3	219	Mean Difference (IV, Fixed, 95% CI)	0.12 [0.08, 0.17]
11.2 Commenced ≥ 24 to < 48 hours	1	96	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.03, 0.09]
12 Weight change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]

12.1 Commenced < 24 hours	1	111	Mean Difference (IV, Fixed, 95% CI)	‐0.22 [‐0.70, 0.26]
12.2 Commenced ≥ 24 to < 48 hours	1	96	Mean Difference (IV, Fixed, 95% CI)	0.27 [‐0.23, 0.77]
13 Head circumference change z‐score to 1 month age Show forest plot	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]

13.1 Commenced < 24 hours	1	135	Mean Difference (IV, Fixed, 95% CI)	0.37 [0.15, 0.59]
13.2 Commenced ≥ 24 to < 48 hours	1	96	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.36, 0.36]
14 Head circumference change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]

14.1 Commenced < 24 hours	1	111	Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.66, 0.36]
14.2 Commenced ≥ 24 to < 48 hours	1	96	Mean Difference (IV, Fixed, 95% CI)	0.4 [‐0.02, 0.82]
15 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

15.1 Commenced < 24 hours	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]
16 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

16.1 Commenced < 24 hours	12	952	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.75, 1.20]
16.2 Commenced ≥ 24 to < 48 hours	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.70, 1.67]
16.3 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	0.70 [0.24, 2.03]
17 Necrotising enterocolitis Show forest plot	14	1301	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.68, 1.47]

17.1 Commenced < 24 hours	12	1083	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.65, 1.49]
17.2 Commenced ≥ 24 to < 48 hours	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.40, 2.95]
18 Chronic lung disease ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

18.1 Commenced < 24 hours	9	723	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.85, 1.19]
18.2 Commenced ≥ 24 to < 48 hours	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.52 [0.79, 2.92]
19 Intraventricular haemorrhage Show forest plot	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]

19.1 Commenced < 24 hours	2	219	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.60, 2.55]
19.2 Commenced ≥ 24 to < 48 hours	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.64, 1.73]
20 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

20.1 Commenced < 24 hours	9	686	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.68, 1.99]
20.2 Commenced ≥ 24 to < 48 hours	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.50, 2.63]
21 Periventricular leukomalacia Show forest plot	7	720	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.24, 1.25]

21.1 Commenced < 24 hours	5	502	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.30, 1.85]
21.2 Commenced ≥ 24 to < 48 hours	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.83]
22 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

22.1 Commenced < 24 hours	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]
23 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

23.1 Commenced < 24 hours	7	574	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.50, 1.51]
23.2 Commenced ≥ 24 to < 48 hours	1	98	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 101.53]
24 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

24.1 Commenced < 24 hours	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]
25 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

25.1 Commenced < 24 hours	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]
26 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

26.1 Commenced < 24 hours	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
27 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

27.1 Commenced ≥ 24 to < 48 hours	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
28 Abnormal serum ammonia > 122 μmol/L Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

28.1 Commenced < 24 hours	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
29 Abnormal blood urea nitrogen (various criteria) Show forest plot	7	689	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.13, 3.60]

29.1 Commenced < 24 hours	4	386	Risk Ratio (M‐H, Fixed, 95% CI)	2.86 [2.01, 4.07]
29.2 Commenced ≥ 24 to < 48 hours	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	2.20 [1.50, 3.23]
29.3 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	10.74 [1.45, 79.59]
30 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]

30.1 Commenced < 24 hours	4	420	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.48, 0.94]
30.2 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.95 [0.18, 20.74]
31 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

31.1 Commenced < 24 hours	4	438	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.92, 1.72]
31.2 Commenced ≥ 24 to < 48 hours	1	96	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.54, 2.45]
32 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

32.1 Commenced < 24 hours	2	291	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.82, 1.64]
32.2 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.35, 4.24]
33 Metabolic acidosis Show forest plot	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

33.1 Commenced < 24 hours	3	220	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.71, 3.72]
33.2 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	8.80 [0.49, 158.47]
34 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

34.1 Commenced < 24 hours	3	409	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.70, 1.61]
34.2 Commenced ≥ 24 to < 48 hours	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.50, 4.18]
34.3 Commenced ≥ 48 to < 72 hours	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	12.70 [0.74, 218.66]

Comparison 8. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to age at commencement

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Comparison 9. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

1.1 Early lipid infusion	12	1161	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.70, 1.20]
1.2 Delayed lipid infusion ≥ 5 days	1	131	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.24, 2.98]
1.3 No lipid infusion	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.31 [0.01, 7.36]
2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

2.1 Early lipid infusion	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]
3 Postnatal growth failure at discharge Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

3.1 Early lipid infusion	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]
4 Days to regain birth weight Show forest plot	13	950	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.73, ‐0.56]

4.1 Early lipid infusion	9	513	Mean Difference (IV, Fixed, 95% CI)	‐2.02 [‐2.73, ‐1.31]
4.2 Delayed lipid infusion ≥ 5 days	2	199	Mean Difference (IV, Fixed, 95% CI)	‐0.57 [‐2.04, 0.91]
4.3 No lipid infusion	2	238	Mean Difference (IV, Fixed, 95% CI)	2.04 [0.58, 3.50]
5 Maximal weight loss (grams) Show forest plot	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]

5.1 Early lipid infusion	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]
6 Maximal weight loss % Show forest plot	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]

6.1 Early lipid infusion	2	59	Mean Difference (IV, Fixed, 95% CI)	‐2.73 [‐5.71, 0.25]
6.2 Delayed lipid infusion ≥ 5 days	1	114	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐1.87, 1.87]
6.3 No lipid infusion	1	115	Mean Difference (IV, Fixed, 95% CI)	0.51 [‐1.66, 2.68]
7 Weight gain g/kg/day to 1 month Show forest plot	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]

7.1 Early lipid infusion	3	250	Mean Difference (IV, Fixed, 95% CI)	0.42 [‐0.94, 1.78]
7.2 No lipid infusion	1	123	Mean Difference (IV, Fixed, 95% CI)	‐4.48 [‐6.17, ‐2.79]
8 Weight gain g/kg/day to discharge Show forest plot	4	291	Mean Difference (IV, Fixed, 95% CI)	0.76 [‐0.02, 1.54]

8.1 Early lipid infusion	3	177	Mean Difference (IV, Fixed, 95% CI)	1.11 [‐0.30, 2.52]
8.2 Delayed lipid infusion ≥ 5 days	1	114	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐0.34, 1.54]
9 Linear growth cm/week up to 1 month age Show forest plot	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.26, ‐0.06]

9.1 Early lipid infusion	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
9.2 No lipid infusion	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]
10 Head circumference growth cm/week up to 1 month age Show forest plot	4	476	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.04, 0.06]

10.1 Early lipid infusion	3	353	Mean Difference (IV, Fixed, 95% CI)	0.07 [0.02, 0.13]
10.2 No lipid infusion	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐0.51, ‐0.24]
11 Head circumference growth cm/week to discharge Show forest plot	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]

11.1 Early lipid infusion	4	315	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.06, 0.13]
12 Weight change z‐score to 1 month Show forest plot	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]

12.1 Early lipid infusion	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]
13 Weight change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]

13.1 Early lipid infusion	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]
14 Weight change z‐score post discharge Show forest plot	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]

14.1 Early lipid infusion	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]
15 Head circumference change z‐score to 1 month Show forest plot	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]

15.1 Early lipid infusion	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]
16 Head circumference change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]

16.1 Early lipid infusion	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]
17 Head circumference change z‐score post discharge Show forest plot	2	201	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐0.14, 0.64]

17.1 Early lipid infusion	2	201	Mean Difference (IV, Fixed, 95% CI)	0.25 [‐0.14, 0.64]
18 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

18.1 Early lipid infusion	10	663	Mean Difference (IV, Fixed, 95% CI)	‐0.24 [‐1.14, 0.66]
18.2 No lipid infusion	1	115	Mean Difference (IV, Fixed, 95% CI)	2.04 [‐3.63, 7.71]
19 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

19.1 Early lipid infusion	12	933	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.79, 1.22]
19.2 Delayed lipid infusion ≥ 5 days	2	199	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.46, 1.71]
19.3 No lipid infusion	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.32, 2.05]
20 Necrotising enterocolitis Show forest plot	14	1301	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.68, 1.47]

20.1 Early lipid infusion	11	932	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.58, 1.43]
20.2 Delayed lipid infusion ≥5 days	1	131	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.15, 7.21]
20.3 No lipid infusion	2	238	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.59, 3.04]
21 Chronic lung disease ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

21.1 Early lipid infusion	8	590	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.98, 1.37]
21.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.24, 1.29]
21.3 No lipid infusion	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.30, 1.24]
22 Patent ductus arteriosus Show forest plot	6	480	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.61, 0.99]

22.1 Early lipid infusion	4	243	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.56, 1.07]
22.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.65, 1.42]
22.3 No lipid infusion	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.20, 1.04]
23 Intraventricular haemorrhage Show forest plot	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]

23.1 Early lipid infusion	2	218	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.70, 1.70]
23.2 No lipid infusion	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.41, 3.91]
24 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

24.1 Early lipid infusion	9	675	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.79, 2.00]
24.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.05, 5.55]
24.3 No lipid infusion	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.31 [0.01, 7.36]
25 Periventricular leukomalacia Show forest plot	7	720	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.24, 1.25]

25.1 Early lipid infusion	5	491	Risk Ratio (M‐H, Fixed, 95% CI)	0.71 [0.26, 1.91]
25.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.07, 16.16]
25.3 No lipid infusion	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.02, 1.52]
26 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

26.1 Early lipid infusion	3	146	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.13, 0.77]
26.2 No lipid infusion	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.27, 9.10]
27 Severe retinopathy of prematurity > stage 2 or treated Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

27.1 Early lipid infusion	6	443	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.53, 1.59]
27.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
27.3 No lipid infusion	1	115	Risk Ratio (M‐H, Fixed, 95% CI)	1.83 [0.17, 19.66]
28 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

28.1 Early lipid infusion	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]
29 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

29.1 Early lipid infusion	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.35, 3.11]
29.2 Delayed lipid infusion ≥ 5 days	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [0.35, 30.19]
30 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

30.1 Early lipid infusion	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
31 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

31.1 Early lipid infusion	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
32 Abnormal serum ammonia Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

32.1 Early lipid infusion	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
33 Abnormal blood urea nitrogen Show forest plot	7	688	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.12, 3.60]

33.1 Early lipid infusion	5	489	Risk Ratio (M‐H, Fixed, 95% CI)	2.66 [1.95, 3.64]
33.2 Delayed lipid infusion ≥ 5 days	2	199	Risk Ratio (M‐H, Fixed, 95% CI)	3.01 [1.83, 4.95]
34 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]

34.1 Early lipid infusion	3	306	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.57, 1.22]
34.2 Delayed lipid infusion ≥ 5 days	2	199	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.18, 0.83]
35 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

35.1 Early lipid infusion	4	420	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.96, 1.73]
35.2 Delayed lipid infusion ≥ 5 days	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.04, 3.22]
36 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

36.1 Early lipid infusion	1	168	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.67, 1.49]
36.2 Delayed lipid infusion ≥ 5 days	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.35, 4.24]
36.3 No lipid infusion	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	1.68 [0.83, 3.41]
37 Metabolic acidosis Show forest plot	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

37.1 Early lipid infusion	2	205	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.71, 3.72]
37.2 Delayed lipid infusion ≥ 5 days	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	8.80 [0.49, 158.47]
37.3 No lipid infusion	1	15	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
38 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

38.1 Early lipid infusion	4	531	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.76, 1.64]
38.2 Delayed lipid infusion ≥ 5 days	1	85	Risk Ratio (M‐H, Fixed, 95% CI)	12.70 [0.74, 218.66]

Comparison 9. Higher versus lower amino acid intake in parenteral nutrition: subgrouped according to lipid intake

Ir a la tabla de la revisión

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 or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality before hospital discharge Show forest plot	14	1407	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.69, 1.17]

1.1 Studies at low risk of bias	5	568	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.42, 1.29]
1.2 Methodological concern	9	839	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.71, 1.30]
2 Neurodevelopmental disability Show forest plot	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]

2.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Methodological concern	2	201	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.48, 2.23]
3 Postnatal growth failure at discharge Show forest plot	3	203	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.56, 0.97]

3.1 Studies at low risk of bias	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.39, 0.88]
3.2 Methodological concern	2	153	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.58, 1.20]
4 Postnatal growth failure post discharge Show forest plot	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]

4.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 Methodological concern	1	111	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.33, 1.32]
5 Days to regain birth weight Show forest plot	13	950	Mean Difference (IV, Fixed, 95% CI)	‐1.14 [‐1.73, ‐0.56]

5.1 Studies at low risk of bias	2	94	Mean Difference (IV, Fixed, 95% CI)	‐0.49 [‐1.87, 0.89]
5.2 Methodological concern	11	856	Mean Difference (IV, Fixed, 95% CI)	‐1.29 [‐1.93, ‐0.64]
6 Maximal weight loss (grams) Show forest plot	3	235	Mean Difference (IV, Fixed, 95% CI)	‐22.71 [‐33.68, ‐11.74]

6.1 Studies at low risk of bias	1	50	Mean Difference (IV, Fixed, 95% CI)	22.60 [‐7.25, 52.45]
6.2 Methodological concern	2	185	Mean Difference (IV, Fixed, 95% CI)	‐29.79 [‐41.58, ‐17.99]
7 Maximal weight loss % Show forest plot	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]

7.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.2 Methodological concern	4	288	Mean Difference (IV, Fixed, 95% CI)	‐0.33 [‐1.61, 0.96]
8 Weight gain g/kg/day up to 1 month age Show forest plot	4	373	Mean Difference (IV, Fixed, 95% CI)	‐1.50 [‐2.56, ‐0.44]

8.1 Studies at low risk of bias	1	122	Mean Difference (IV, Fixed, 95% CI)	1.5 [‐0.27, 3.27]
8.2 Methodological concern	3	251	Mean Difference (IV, Fixed, 95% CI)	‐3.16 [‐4.48, ‐1.84]
9 Weight gain g/kg/day to discharge Show forest plot	4		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

9.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Methodological concern	4	291	Mean Difference (IV, Fixed, 95% CI)	0.76 [‐0.02, 1.54]
10 Linear growth cm/week up to 1 month age Show forest plot	2	245	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐0.26, ‐0.06]

10.1 Studies at low risk of bias	1	122	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.15, 0.15]
10.2 Methodological concern	1	123	Mean Difference (IV, Fixed, 95% CI)	‐0.27 [‐0.40, ‐0.14]
11 Head circumference growth cm/week up to 1 month age Show forest plot	5	562	Mean Difference (IV, Fixed, 95% CI)	0.07 [0.03, 0.11]

11.1 Studies at low risk of bias	2	257	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.02, 0.15]
11.2 Methodological concern	3	305	Mean Difference (IV, Fixed, 95% CI)	0.06 [0.02, 0.10]
12 Head circumference growth cm/week to discharge Show forest plot	3	229	Mean Difference (IV, Fixed, 95% CI)	0.07 [0.02, 0.11]

12.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
12.2 Methodological concern	3	229	Mean Difference (IV, Fixed, 95% CI)	0.07 [0.02, 0.11]
13 Weight change z‐score up to 1 month age Show forest plot	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]

13.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
13.2 Methodological concern	1	96	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.62, 0.22]
14 Weight change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]

14.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
14.2 Methodological concern	2	207	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.33, 0.36]
15 Weight change z‐score post discharge Show forest plot	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]

15.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
15.2 Methodological concern	2	201	Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.26, 0.52]
16 Head circumference change z‐score up to 1 month Show forest plot	2	231	Mean Difference (IV, Fixed, 95% CI)	0.27 [0.08, 0.46]

16.1 Studies at low risk of bias	1	135	Mean Difference (IV, Fixed, 95% CI)	0.37 [0.15, 0.59]
16.2 Methodological concern	1	96	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.36, 0.36]
17 Head circumference change z‐score to discharge Show forest plot	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]

17.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
17.2 Methodological concern	2	207	Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.15, 0.50]
18 Head circumference change z‐score post discharge Show forest plot	1	111	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.46, 0.52]

18.1 Studies at low risk of bias	0	0	Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
18.2 Methodological concern	1	111	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.46, 0.52]
19 Days to full enteral feeds Show forest plot	11	778	Mean Difference (IV, Fixed, 95% CI)	‐0.19 [‐1.07, 0.70]

19.1 Studies at low risk of bias	3	169	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐1.60, 1.20]
19.2 Methodological concern	8	609	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐1.32, 0.97]
20 Late‐onset sepsis Show forest plot	15	1255	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.79, 1.18]

20.1 Studies at low risk of bias	4	461	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.71, 1.25]
20.2 Methodological concern	11	794	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.73, 1.31]
21 Necrotising enterocolitis Show forest plot	14	1428	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.65, 1.33]

21.1 Studies at low risk of bias	5	511	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.50, 1.60]
21.2 Methodological concern	10	917	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.60, 1.50]
22 Chronic lung disease at ≥ 36 weeks' PMA Show forest plot	10	819	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.89, 1.23]

22.1 Studies at low risk of bias	2	177	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.79, 1.31]
22.2 Methodological concern	8	642	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.86, 1.30]
23 Intraventricular haemorrhage Show forest plot	3	341	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.74, 1.69]

23.1 Studies at low risk of bias	1	122	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.64, 1.73]
23.2 Methodological concern	2	219	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.60, 2.55]
24 Severe intraventricular haemorrhage Show forest plot	11	904	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.74, 1.82]

24.1 Studies at low risk of bias	4	343	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.66, 3.03]
24.2 Methodological concern	7	561	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.59, 1.81]
25 Periventricular leukomalacia Show forest plot	7	720	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.24, 1.25]

25.1 Studies at low risk of bias	3	299	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.21, 1.81]
25.2 Methodological concern	4	421	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.13, 1.69]
26 Retinopathy of prematurity Show forest plot	4	269	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.21, 0.93]

26.1 Studies at low risk of bias	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	0.16 [0.04, 0.67]
26.2 Methodological concern	3	194	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.33, 2.22]
27 Severe retinopathy of prematurity (> stage 2 or treated) Show forest plot	8	672	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.56, 1.63]

27.1 Studies at low risk of bias	3	252	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.36, 1.66]
27.2 Methodological concern	5	420	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.57, 2.55]
28 Cerebral palsy Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]

28.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
28.2 Methodological concern	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	4.0 [0.89, 17.97]
29 Developmental delay at ≥ 18 months Show forest plot	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]

29.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
29.2 Methodological concern	3	301	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.52, 3.53]
30 Blindness Show forest plot	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]

30.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
30.2 Methodological concern	2	122	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.20, 19.91]
31 Deafness Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

31.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
31.2 Methodological concern	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
32 Abnormal serum ammonia > 122 μmol/L Show forest plot	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]

32.1 Studies at low risk of bias	1	61	Risk Ratio (M‐H, Fixed, 95% CI)	3.10 [0.13, 73.16]
32.2 Methodological concern	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
33 Abnormal blood urea nitrogen Show forest plot	7	688	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [2.12, 3.60]

33.1 Studies at low risk of bias	2	183	Risk Ratio (M‐H, Fixed, 95% CI)	12.29 [1.66, 90.79]
33.2 Methodological concern	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	2.57 [1.97, 3.34]
34 Hyperglycaemia, plasma glucose > 8.3 mmol/L Show forest plot	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]

34.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
34.2 Methodological concern	5	505	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.49, 0.96]
35 Hyperglycaemia treated with insulin Show forest plot	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]

35.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
35.2 Methodological concern	5	534	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.93, 1.66]
36 Hypoglycaemia Show forest plot	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]

36.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
36.2 Methodological concern	3	376	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.84, 1.63]
37 Metabolic acidosis Show forest plot	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]

37.1 Studies at low risk of bias	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
37.2 Methodological concern	4	305	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [0.94, 4.47]
38 Cholestasis Show forest plot	5	616	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.86, 1.84]

38.1 Studies at low risk of bias	2	249	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.67, 2.17]
38.2 Methodological concern	3	367	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.79, 2.13]

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