Uthaya 2016.
| Methods | Design: NEON (Nutritional Evaluation and Optimisation in Neonates), a 2 × 2 factorial, double‐blind, multicentre RCT Setting: 4 National Health Service NICUs in London and southeast England I. Allocation concealment: yes II. Blinding of intervention: yes III. Blinding of outcome measurement(s): yes IV. Complete follow‐up: yes |
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| Participants | Inclusion: preterm infants < 31 weeks' gestation Exclusion: life‐threatening abnormalities and those for whom study authors were unable to administer trial PN within 24 hours of birth. When possible, the trial was discussed with parents antenatally, and written informed consent was sought within 24 hours of birth |
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| Interventions | The infants were randomised to one of four groups: Group 1: Inc‐AA/S‐LE (20% Intralipid); n = 42; Group 2: Inc‐AA/SMOF (20% SMOFLipid); n = 42; Group 3: Imm‐RDI/S‐LE (20% Intralipid); n = 41; Group 4: Imm‐RDI/SMOF; (20% SMOFLipid) n = 43; Inc‐AA infants received 1.7 g/kg amino acids on day 1, 2.1 g/kg on day 2, and a maximum of 2.7 g/kg/d from day 3; Imm‐RDI infants received 3.6 g/kg/d amino acids from day 1. PN within 24 hours of birth to trial PN ceased when an infant had received and tolerated 150 mL milk/kg/d21 for at least 24 hours. |
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| Outcomes | Primary outcomes: non‐adipose mass for the amino acid intervention and intrahepatocellular lipid for the lipid intervention using MRI and MR spectroscopy. Study evaluated prespecified safety measures (serum lipids, cholesterol, creatinine, urea, bilirubin, liver function tests, blood glucose, and base deficit) from routine clinical tests. | |
| Notes | Well‐designed trial with collaboration from various trial units in London and overseen by the Imperial College London Clinical Trials Unit. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "incorporated minimization with a random element." The trial was managed by the Imperial College London Clinical Trials Unit. This may also add to validity of the trial procedures. Comment: done |
| Allocation concealment (selection bias) | Low risk | Quote: "use of an interactive voice recognition telephone system to 1 of 4 groups (Inc‐AA/SO, Inc‐AA/SMOF, Imm‐RDI/SO, and Imm‐RDI/SMOF) and incorporated minimization with a random element and stratification by gestational age (23 to 26 or 27 to 31 completed weeks), birth weight (< 500, 500 to 1000, or > 1000 g), and centre." Comment: done |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Trial formulations were investigational medicinal products prepared by a licensed facility (Bath ASU). Other PN components were identical across randomized groups." "Hospital pharmacy staff dispensed trial PN between 0900 and 1700; attending clinicians were blinded to trial allocation." Comment: done |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: "Image analysis with the use of Slice‐O‐Matic (version 4.2; Tomovision) was undertaken independently by the Vardis Group and was blinded to participant identity and group allocation." Quote: review authors agreed that the risk was low. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: The primary and most other clinical outcomes are available for most participants. The authors also provided detailed information about outcomes for all participants and for those infants completing magnetic resonance assessment. Comment: done |
| Selective reporting (reporting bias) | Low risk | Quote: "ISRCTN29665319; EudraCT 2009‐016731‐34" Comment: no concerns regarding reporting bias. |
| Other bias | Low risk | Comment: none. |