Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial

Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants. Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point. Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections). Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.