Abstract: Eight trials recruiting a total of 637 infants met the inclusion criteria for the systematic review. The infants included in the review were mainly formula-fed term infants. The trials were of variable methodological quality. Formula-fed term infants with GOR on feed thickeners had nearly two fewer episodes of regurgitation per day (mean difference -1.97 episodes per day, 95% confidence interval (CI) -2.32 to -1.61; 6 studies, 442 infants, moderate-certainty evidence) and were 2.5 times more likely to be asymptomatic from regurgitation at the end of the intervention period (risk ratio 2.50, 95% CI 1.38 to 4.51; number needed to treat for an additional beneficial outcome 5, 95% CI 4 to 13; 2 studies, 186 infants, low-certainty evidence) when compared to infants with GOR on unthickened feeds. No studies reported failure to thrive as an outcome. We found low-certainty evidence based on 2 studies recruiting 116 infants that use of feed thickeners improved the oesophageal pH probe parameters of reflux index (i.e. percentage of time pH < 4), number of reflux episodes lasting longer than 5 minutes, and duration of longest reflux episode. No major side effects were reported with the use of feed thickeners. Information was insufficient to conclude which type of feed thickener is superior. Gastro-oesophageal reflux is a physiological self resolving phenomenon in infants that does not necessarily require any treatment. However, we found moderate-certainty evidence that feed thickeners should be considered if regurgitation symptoms persist in term bottle-fed infants. The reduction of two episodes of regurgitation per day is likely to be of clinical significance to caregivers. Due to the limited information available, we were unable to assess the use of feed thickeners in infants who are breastfeeding or preterm nor could we conclude which type of feed thickener is superior.

Plain-language summary: We examined the research published up to 22 November 2016. We found 8 clinical trials recruiting 637 babies up to 6 months of age who presented with symptoms of GOR. The recruited babies were mainly 'healthy' term babies (i.e. babies born within three weeks of the due date) who were bottle feeding. Three of the studies were funded by a pharmaceutical company, hence the quality of the evidence presented must be interpreted with caution. We found that term babies with GOR given feed thickeners had nearly two fewer reflux episodes per day. Babies with GOR were also 2.5 times more likely to have no reflux symptoms if feed thickeners were used. No studies reported information on failure to thrive (i.e. poor growth). We found that babies with GOR given feed thickeners showed an improvement in an important measure of acid reflux obtained from pH study. Reflux index (i.e. percentage of time of acidic reflux of pH < 4) was 5% lower in babies given feed thickeners. No major harms were reported in the eight studies. Due to study design limitations, we are moderately confident in the evidence for the reduction of two reflux episodes per day. Hence, feed thickeners can be useful in term babies who are bottle feeding and have troublesome GOR. We rated the quality of the evidence for the other outcomes as low due to the small number of studies with small numbers of babies recruited. Further research is needed to determine which type of feed thickener is better and whether feed thickeners are useful in babies with GOR who are breastfeeding or preterm.