Abstract: Three small studies evaluating 154 infants were included in this review. One study reported a significant reduction in the risk of hyperbilirubinaemia and rate of treatment with phototherapy associated with enteral supplementation with prebiotics (risk ratio (RR) 0.75, 95% confidence interval (95% CI) 0.58 to 0.97; one study, 50 infants; low-quality evidence). Meta-analyses of two studies showed no significant difference in maximum plasma unconjugated bilirubin levels in infants with prebiotic supplementation (mean difference (MD) 0.14 mg/dL, 95% CI -0.91 to 1.20, I² = 81%, P = 0.79; two studies, 78 infants; low-quality evidence). There was no evidence of a significant difference in duration of phototherapy between the prebiotic and control groups, which was only reported by one study (MD 0.10 days, 95% CI -2.00 to 2.20; one study, 50 infants; low-quality evidence). The meta-analyses of two studies demonstrated a significant reduction in the length of hospital stay (MD -10.57 days, 95% CI -17.81 to -3.33; 2 studies, 78 infants; I² = 0%, P = 0.004; low-quality evidence). Meta-analysis of the three studies showed a significant increase in stool frequency in the prebiotic groups (MD 1.18, 95% CI 0.90 to 1.46, I² = 90%; 3 studies, 154 infants; high-quality evidence). No significant difference in mortality during hospital stay after enteral supplementation with prebiotics was reported (typical RR 0.94, 95% CI 0.14 to 6.19; I² = 6%, P = 0.95; 2 studies; 78 infants; low-quality evidence). There were no reports of the need for exchange transfusion and incidence of acute bilirubin encephalopathy, chronic bilirubin encephalopathy, and major neurodevelopmental disability in the included studies. None of the included studies reported any side effects. Current studies are unable to provide reliable evidence about the effectiveness of prebiotics on hyperbilirubinaemia. Additional large, well-designed RCTs should be undertaken in neonates that compare effects of enteral supplementation with prebiotics on neonatal hyperbilirubinaemia with supplementation of milk with any other placebo (particularly distilled water) or no supplementation.

Plain-language summary: We included three small studies (with a total of 154 infants) that compared the effects of feeding supplementation with prebiotics on neonatal jaundice to a placebo (such as distilled water). The evidence is up to date as of 14 June 2018. There is inadequate evidence to assess the effectiveness of prebiotics on neonatal jaundice. According to the available data, the incidence of neonatal hyperbilirubinaemia (low-quality evidence) and treatment with phototherapy (low-quality evidence) were decreased by feeding supplementation with prebiotics, but only one small study reported on these outcomes. The meta-analyses of these small studies demonstrated a significant reduction in the length of hospital stay (low-quality evidence) and a significant increase in stool frequency (high-quality evidence) in infants with prebiotic supplementation versus placebo. Furthermore, meta-analyses showed no significant difference in maximum plasma bilirubin levels (low-quality evidence), duration of phototherapy (low-quality evidence) and neonatal mortality (low-quality evidence) between groups. The review found only three randomised clinical trials that compared prebiotic supplementation with a placebo. More research is needed.