Probiotics for the management of neonatal hyperbilirubinemia: a systematic review of randomized controlled trials

BACKGROUND: Neonatal jaundice requiring phototherapy is associated with significant socioeconomic burden including hospital readmission, prolonged hospital stay, and separation of the baby from mother.

OBJECTIVES: To assess the efficacy and safety of probiotics in reducing the need for phototherapy and its duration in neonatal hyperbilirubinemia.

METHODS: A systematic review of randomized controlled trials (RCTs) of probiotic supplementation for prevention or treatment of jaundice in neonates (any gestation or weight) using the Cochrane methodology. Primary outcome was the duration of phototherapy. Secondary outcomes included incidence of jaundice, total serum bilirubin (TSB) level at 24, 48, 72, 96 h, and day 7, duration of hospital stay, and adverse effects (e.g. probiotic sepsis). Results were summarized as per GRADE guidelines.

RESULTS: Nine RCTs (prophylactic: six trials, N = 1761; therapeutic: three trials, N = 279) with low to high risk of bias were included. Meta-analysis (random-effects model) showed probiotic supplementation reduced duration of phototherapy [N = 415, mean difference (MD): -11.80 (-17.47, -6.13); p < .0001; level of evidence (LOE): low]. TSB was significantly reduced at 96 h [MD: -1.74 (-2.92, -0.57); p = .004] and 7 d [MD: -1.71 (-2.25, -1.17); p < .00001; LOE: low] after probiotic treatment. Prophylactic probiotics did not reduce the incidence of jaundice significantly [N = 1582, relative risk (RR): 0.56 (0.25, 1.27); p = .16; LOE: low]. There were no probiotic-related adverse effects.

CONCLUSION: Limited low-quality evidence indicates that probiotic supplementation may reduce the duration of phototherapy in neonates with jaundice. Routine use of probiotics to prevent or treat neonatal jaundice cannot be recommended. Large well-designed trials are essential to confirm these findings.