Methods

Randomised controlled trial

Participants

80 children of gestational age > 30 weeks and chronological age < 2 years

Exclusion criteria: renal or hepatic dysfunction, an inborn error of metabolism, immunodeficiency, use of corticosteroids, pre‐existent life expectancy < 6 months, and simultaneous participation in another trial
Setting: Sophia Children's Hospital/Erasmus Medical Centre, Rotterdam, the Netherlands
1 infant was withdrawn from the study within 3 days post‐randomisation when it became clear that enteral feeding would be well tolerated. This infant was not included in any intention‐to‐treat analyses.

Interventions

Intervention (n = 41): on the second postoperative day infants in the intervention group received a standard parenteral nutrition solution supplemented with L‐glutamine sufficient to provide 0.4 g/kg/day.

Control (n = 39): infants received parenteral nutrition with an iso‐nitrogenous amino acid solution.
The protocol specified that participating infants should continue to receive full parenteral nutrition until at least the 6th postoperative day when enteral feeding was gradually re‐introduced.

Outcomes

1. Intestinal permeability (sugar absorption test)
2. Nitrogen balance
3. Death prior to hospital discharge
4. Length of intensive care unit and hospital stay
5. Episodes of invasive infection
6. Use of antibiotics

Notes

This trial did not strictly fulfil our a priori population criterion of including only infants < 3 months old. However, we made a consensus decision to include the trial because the report stated that most (69 of the 80) participants were < 6 months old at enrolment. We have contacted the trial investigator to determine whether outcome data are available for infants less than 3 months old.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated, blocks of 4

Allocation concealment (selection bias)

Low risk

Randomisation schedule available only to pharmacist

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Physicians and nurses blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data were analysed by intention‐to‐treat

Methods

Randomised controlled trial

Participants

20 infants with significant gastrointestinal illness including NEC requiring laparotomy and resection, intestinal atresia, omphalocoele, gastroschisis, intestinal volvulus, or malrotation

Exclusion criteria: significant hepatic, renal, or metabolic disease necessitating protein restriction < 1.0 g/kg/day; significant extra‐intestinal disease (cystic fibrosis, severe hypoxic ischaemic encephalopathy); or extreme short bowel syndrome (defined as < 25 cm of residual bowel length)
Setting: Children's Hospital, Boston, USA

Interventions

Intervention (n = 9): glutamine‐supplemented (up to 0.31 g/kg/day) expressed human milk or hydrolysed formula milk
Control (n = 11): human milk or formula without added glutamine
The study milk was introduced when infants were assessed as ready to tolerate enteral feeding and continued until day 30

Outcomes

1. Time taken to establish full enteral feeding
2. Rates of nosocomial infection
3. Growth during the study period
4. In hospital mortality (personal communication from trial investigators)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random numbers list in blocks of 4

Allocation concealment (selection bias)

Low risk

Sealed envelopes, opened by hospital pharmacists

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Investigators, parents, physicians, nurses blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

> 80% followed up

Methods

Randomised controlled trial

Participants

174 infants with significant gastrointestinal illness, including abdominal wall defect, congenital bowel obstruction, and NEC

Exclusion criteria: renal failure, inborn errors of metabolism or immune deficiency

Setting: 14 paediatric surgical units in the UK

Interventions

Intervention (n = 87): parenteral nutrition supplemented with glutamine dipeptide (0.6 g/kg/d)

Control (n = 87): isonitrogenous, isocaloric parenteral nutrition solution

Outcomes

1. Time on parenteral nutrition

2. Time to full enteral feeding

3. Incidence of sepsis and septicaemia

Adverse events and mortality also reported

Notes

This trial was stopped when funding came to an end before the target of 250 participants was achieved. It was judged that there was a less than 5% chance of identifying the specified differences in the primary outcome measure (duration of parenteral nutrition), even if recruitment had continued as planned.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Methods used to generate sequence in pharmacy not stated explicitly

Allocation concealment (selection bias)

Low risk

Infants allocated to groups by central pharmacy, allocation communicated to pharmacy of recruiting centre and not shared outside of pharmacy

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Parents, nurses, physicians, surgeons, and trial coordinator blinded

Allocation was revealed in one case (control group) where clinically necessary

Incomplete outcome data (attrition bias)
All outcomes

Low risk

> 80% followed up, any loss to follow‐up explained and balanced across groups

4 infants in each group who had "intervention discontinued" were not included in final analyses by intention to treat