Evaluation of the Safety of an Infant Formula Containing Bifidobacterium Breve PS1, a Strain Isolated From Human Milk, in a Pilot Trial.

Introduction Some perinatal circumstances, such as the mode of birth, can alter the composition of the infant gut microbiota. As an example, infants born by caesarean section are prone to gut dysbiosis (including a depletion of bifidobacteria) in comparison with those born by vaginal delivery, leading to an increased rate of gastrointestinal and respiratory tract infections. Interestingly, breastfeeding can restore the Bifidobacterium population, which in turn was associated with a decrease in the rate of various infections.

Despite the important functions that bifidobacteria may play in the infant gut, some studies have shown that these bacteria may be present at a low concentration or even ab-sent in some infants. Some factors, including lack of breastfeeding, early weaning, maternal/infant antibiotic therapy or HMO composition may select against bifidobacteria in the mother-infant dyad. Therefore, there is a need for strategies to develop functional foods, including infant formula, to provide bifidobacterial strains naturally present in human milk to infants who may be deprived of such microbes. In this context, the objectives of this work were, first, to characterize of the potential probiotic properties of a bifidobacterial strain isolated from human milk and, subsequently, to test its safety and tolerance in a population of 3-months-old formula-fed infants

Materials and Methods Study Design A randomized double-blinded controlled intervention study with two study groups was carried out. Healthy, three month old infants, who due to their mothers' choice were exclusively formula-fed from birth, were recruited into the study after informed written consent was obtained from the parents. Investigators took special precautions and care throughout their communication with the families in order to support and protect, and not to discourage breastfeeding, and not to suggest bottle feeding to parents of a breastfed baby. The exclusion criteria included history of mild or serious gastrointestinal disorders (history of chronic diarrhea or constipation, gastroesophageal reflux), gastrointestinal surgery, cow's milk protein allergy, metabolic disorders (diabetes, lactose intolerance), immune deficiency, antibiotic prescription three-weeks prior to inclusion and previous use of probiotic-containing formula. Exclusion criteria during the study were lack of compliance with the study protocol, adverse events related to the consumption of the study formula, not attending scheduled visits to the primary care center, and severe regurgitation and/or colic that, according to pediatricians, needed prescription of a special formula.

The protocol was approved by the Ethics Committee of the Hospital Clínico (Madrid, Spain) (Reference 10/017-E).

Sample size Sample size was estimated based on the primary outcome of average weight gain of infants between baseline visit and visit 1 (180 ± 5 days of age). Based on previous publications where growth was the primary outcome variable as part of a safety study, the study was designed to have a power to detect a difference in weight gain equal to 0.5 standard deviations. Thus, at least 65 children would be needed in each formula group under the assumption of non-inferiority (one-sided test), with a significance level of 2.5% and power of 80%.