Immunity Modification of Full Term Infants According to the Type of Feeding and Mode of Delivery
Condition: Innate Immunity; Newborns; Nutrition; Microbiota
Study type: Interventional

Summary: 
      This is a single-center, double-blind, randomized controlled trial, with parallel groups and
      reference group. The aim of the study was to investigate whether feed a fermented formula
      milk leads to an increase of anti-microbial peptides such as catelecidine, alpha and beta
      defensins and secretory-IgA, compared to feed a standard formula (Plasmon Primigiorni),
      according to mode of delivery. Breastfed infants were the reference group.
    

Detailed description: 
      The microbiota plays an important role in modulating the development of the immune system,
      making decisive the interrelation that between nutrition, microbiota and immune cells to
      modulate long-term health outcomes.

      The type of feeding, especially breastfeeding, and the type of delivery are factors that can
      contribute to the development of the microbiota. Specifically, the exclusive breastfeeding
      promotes the development of bifidobacteria that promotes protection against potential
      infections and the development of the immune system.

      In recent years it was improved the biological effects of formula milk, that represent the
      substitutes of breast milk when this is not available or if there are contraindications to
      breastfeeding. Functional foods derived from fermentation of cow's milk with probiotic
      strains have been proposed for the prevention of infectious diseases of the child. Recently,
      in a monocentric double-blind prospective study, the efficacy of fermented cow's milk with
      Lactobacillus paracasei CBA L74 was evaluated in the prevention of common winter infections
      in children aged between 12 and 48 months. In this study, children treated with fermented
      milk had a lower incidence of respiratory and gastrointestinal tract infections compared to
      the control group. This effect was associated with a significant stimulation of innate
      immunity (α- and β-defensin, LL-37) and acquired (secretory IgA) and to a modulation of
      composition and function of the intestinal microbiota characterized by a significant increase
      in strains producing butyric acid (Firmicutes phyla). The nutritional intervention was very
      well accepted by the children and no adverse events were observed.

      Primary objectives of this study were:

      To evaluate whether the feeding with a fermented formulated milk determines an increase in
      anti-microbial peptides such as catelecidine, alpha and beta defensin and secretory IgA
      compared to the feed with the standard formula (Plasmon Primigiorni), with reference to the
      mother's milk.

      Secondary objective:

        -  Value the tolerance in the two groups of infants fed with the two formulas in the study,
           with reference to the group of infants fed with breast milk.

        -  Value the modifications of the intestinal microbiota in the two groups of infants fed
           with the two formulas in the study, with reference to the group of infants fed with
           breast milk.

      Study design: Single-center, randomized, double-blind, parallel group study with reference
      group.

      Methods:

        -  Evaluation of the anthropometric parameters (weight, length and cranial circumference)

        -  Evaluation of body composition by plethysmography

        -  Evaluation of the gastrointestinal tolerance of fermented formulated milk by means of
           data collection and diary delivery to the parents of the participants

        -  Evaluation of the safety of fermented formulated milk by recording adverse events

        -  Determination of faecal samples of antimicrobial peptides (defensins, catelecidines),
           IgA, microbiota and metabolome.

      Infants will be enrolled at birth (within 7 days of life) upon acquisition of the informed
      consent of both parents.

      At the time of enrollment, newborns who take breast milk due to the absence of breast milk
      will be randomized to receive up to the third month of age or a fermented formulated milk or
      a standard formula (Plasmon First Days).

      Enrollment will be carried out by promoting and supporting breastfeeding and, in the event of
      exclusive breastfeeding forecasts for at least the first 3 months of age, newborns will be
      included in the study as a control group.

      There are 3 medical visits to enrollment (V0), the first (V1) and the third month of life
      (V2).

      During the visits the anthropometric parameters, the body composition, and the gastroenteric
      tolerance will be evaluated. A stool sample will also be collected at the three points of the
      life study in order to determine the anti-microbial peptides (catelecidine, alpha and beta
      defensin) and the secretory IgA, and perform the analysis of the microbiota and the
      metabolome.

      Statistical analysis:

      The sample size was determined to identify between the two groups of infants, the one that
      received the fermented formulated milk and the one that received standard formulated milk
      (Plasmon Primigiorni), a difference in the content of faecal α-defensins on samples of feces.
      Considering the results of the effect of a treatment with milk fermented with L. paracasei
      CBA L74 on fecal α-defensins in children attending preschool centers mean value (DS) vs
      placebo [4.8 (4.2) vs 1 (0.6), respectively] we calculated that 12 newborns are needed per
      group with a power of 84% and an alpha of 0.05. Assuming a 30% drop-out rate, at least 16
      newborns per group must be recruited.

      Criteria for the evaluation of variables The descriptive analyzes will be performed by
      calculating mean, median and standard deviations for the continuous variables and expressing
      the distribution of the frequencies for the discrete variables. The main analysis will resort
      to tests for independent samples, Student or Mann-Whitney tests according to the distribution
      of the outcome variables. To jointly analyze the trend in time from V0 to V2 of the outcome
      variables in the two groups, the one that received the fermented formulated milk and the one
      that received the standard formula, based on the type of delivery (spontaneous or cesarean)
      will be used regression models for repeated measurements (random effects models or GEE
      models).
    

Intervention name(s): Feeding infants with fermented formula milk; Feeding infants with standard formula milk; Breastfeeding infants
Intervention type(s): Dietary Supplement; Other; Other
Intervention description(s): Infants enrolled were fed either with fermented formula milk or with standard formula during the first four months of life. Breastfed infants were the reference group.; Infants enrolled were fed either with fermented formula milk or with standard formula during the first four months of life. Breastfed infants were the reference group.; Reference group
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: RCT double blind study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Newborns; Fermented milk; Innate immunity