Characteristics of included studies
| Studies | Corvagliaet al 12 | Corvaglia et al 13 | Davidson et al 15 | Omari et al 11 | Orenstein et al 14 | Wheatley and Kennedy10 |
| Methods | Clinical trial—crossover of treatment and placebo | Clinical trial—crossover of treatment and placebo | Randomised, double-blind, placebo controlled trial | Randomised, double-blind, placebo-controlled, crossover design trial | Multicentre, double-blind, randomised, placebo-controlled trial | Randomised, controlled, blind crossover study of treatment and placebo |
| Participants | 32 Preterm newborns (gestational age≤33 weeks) | 28 Preterm newborns (gestational age≤33 weeks) | 52 Term infants or with a gestational or postconceptional age of 28–44 weeks | 10 Preterm infants with a mean postmenstrual age of 36.1±0.7 (range, 34–40 weeks) | 162 Infants aged 16 weeks (median, range 4–51) gestation at birth 35 weeks (median, range 25–39) | 18 Preterm<37 weeks and corrected gestational age at enrolment<44 weeks |
| Diagnostic symptoms | Frequent regurgitations and/or postprandial desaturations) | Recurrent postprandial apnoeas | Two of the following clinical findings: apnoea±bradycardia; ±oxygen desaturations, vomiting or gagging, and irritability or pain at least every second feed or at least twice every 8 hours | Infants with symptoms of GORD, confirmed by 24 hour pH monitoring with significant reflux index | Infants with symptomatic GORD who remained symptomatic within 1 hour after feeding despite at least 1 week of non-pharmacological management | Clinical diagnosis of GOR and bradycardia attributed to GOR by clinicians |
| Interventions | 0.25 mL/kg sodium alginate was given four times at alternate meals (DG meals), remaining four meals were placebo (DF meals) | 0.25 mL/kg sodium alginate after one single meal (DG meal) or placebo (DF meal) | Esomeprazole 0.5 mg/kg or placebo once daily for up to 14 days | Omeprazole (0.7 mg/kg) or placebo (days 1–7) and then the alternative treatment regimen was given for the second week (days 8–14) | Lansoprazole administered once daily at 0.2–0.3 mg/kg/day for infants age≤10 weeks and at 1.0–1.5 mg/kg/day for those age>10 weeks or placebo (maximum 4 weeks of study drug treatment) | Metoclopramide (0.2 mg/kg/dose every 6 hours) and ranitidine (2 mg/kg/dose) every 8 hours or placebo. Each infant was randomly assigned to one of two study groups |
| Primary outcomes | GOR features (ie, number, acidity, duration and height of GORs) | Apnoea episodes and gastro-oesophageal features | Change from baseline to end of treatment in the total number of GORD-related symptoms and signs (vomiting, apnoea, bradycardia, oxygen desaturation, gagging, back arching, irritability, crying and fussing) | Gastric acidity, oesophageal acid exposure and the number and duration of acid reflux episodes | Number and duration of crying episodes during or ≤1 hour after feeding and frequency of various GORD symptoms quantified in daily diaries | Bradycardia episodes per day |
| Secondary outcomes | NS | NS | Adverse events | Number of vomiting, apnoea, bradycardia or behavioural changes | Adverse events | NS |
DF, drug-free; DG, drug-given; GOR, gastro-oesophageal reflux; GORD, gastro-oesophageal reflux disease; NS, not specified.