Effect of an Infant Formula With Synbiotics in Infants Born Via Caesarean Section

Study Overview
=================
Brief Summary
-----------------
A multi-centre, randomized, parallel-group, double-blind, controlled, exploratory clinical trial is conducted to assess the positive effect of feeding a formula containing synbiotics (pre- and probiotics) on the composition of the gut microbiota in caesarean section (CS) born healthy term infants within the first 6 months of life.

Detailed Description
-----------------
Since caesarean section (CS)-born infants show dysbiotic microbial colonization during the first weeks of life, exclusive breastfeeding is the feeding mode of choice for these infants. However, since CS births are often associated with breast-feeding difficulties, it is of importance to feed an microbiota-supportive infant formula. This study is designed to investigate whether an infant formula supplemented with synbiotics positively affects the microbial composition, gastrointestinal characteristics and the proper function of the immune system in CS-born infants, compared to feeding a standard infant formula without synbiotics in either CS- and vaginal-born infants during the first 6 months of life. The growth of the infants as well as tolerance, infectious diseases and allergies will also be assessed. In order to investigate the effect of different birth modes and feeding conditions on the microbiota, the study population will include healthy term infants, born either by CS or by VD, additional groups receive human milk or formula with prebiotics only. Additionally, if the parents agree, their infant will be followed up until 24 months of age with a special focus on the prevention of infections and allergies.

Official Title
-----------------
Evaluation of the Effect of an Infant Formula Containing Synbiotics on the Composition of the Gut Microbiota in Infants Born Via Caesarean Section

Conditions
-----------------
Gut Microbiota

Intervention / Treatment
-----------------
* Other: Intervention Group 1: Infant Formula with synbiotics
* Other: Intervention Group 2: Infant Formula with prebiotics
* Other: Control Group 1 and 2: Infant Formula without synbiotics


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy term infants Female or male gender Gestational age ≥37 weeks, <42 weeks Singleton, born by caesarean section or vaginally born Birth weight between ≥2500g and ≤4200g with a regular weight gain without any signs of developmental delays or growth disorders according to investigator opinion Uncomplicated early course of neonatal period Age at enrolment: 5 +/-1 days of life Infants whose parent(s)/ legal authorized representatives (LAR(s)) have reached the legal age of majority in Bulgaria Infants whose parent(s)/ LAR(s) are capable of and willing to comply with the protocol and have signed the informed consent form in accordance with legal requirements At least one of the legal representatives is affiliated to a health security/insurance or equally Infants whose parent(s)/ LAR(s) are willing to comply with the feeding regimen during the intervention period. Infant's parent(s)/ LAR(s) will decide which feeding regimen will be used (infant formula or breast milk) Parents/ LARs who agree to not use any sort of other formula than provided during the study Exclusion Criteria: Intensive care prior to or at Baseline Visit UV-treatment of jaundice and clinical significant jaundice prior to Baseline Visit (according to investigator opinion) Known immune deficiency Serious acquired or congenital diseases, chromosomal anomalies (if known) Serious pre-natal and/or serious post-natal disease before enrolment (per investigator's medical diagnosis) Infants or mothers under antibiotic treatment before Baseline Visit (only for vaginally born and breastfed infants) or at Baseline Visit (all groups) Infants requiring infant formula intake other than those specified in the protocol (formula for special medical purposes (FSMP), formula with hydrolyzed protein (allergy risk) Infant's supplementation or formula intake, which contains probiotics, prebiotics, dietary fibres or synbiotics before and during study Feeding difficulties or formula intolerance according to investigator's opinion Currently participating or having participated in another clinical trial since birth Reason to presume that the infant's parent(s)/LAR(s) are unable to meet the study plan requirements, such as drug/alcohol abuse, psychological or linguistic incapability, chronic or mental diseases Infants born to mothers with medical conditions that require prescription medication (coagulation abnormalities, if acetylsalicylic acid was not stopped at 35 weeks GA according to guidelines, mothers treated with Methyldopa, ACE inhibitors, breastfeeding mothers treated with L-thyroxine, diabetic mothers, epileptic mothers) Any smoking, drug or alcohol intake by the mother during the last two trimesters of pregnancy Mother's weight gain >18 kg during pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 4 Days
Maximum Age: 6 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Infant Formula with synbiotics (CS-born)<br>CS born infants, randomized to receive infant formula with synbiotics | Other: Intervention Group 1: Infant Formula with synbiotics<br>* Infants will receive infant formula during the first 6 months of life<br>|
| Experimental: Standard Infant Formula with prebiotics (CS-born)<br>CS born infants, randomized to receive infant formula with prebiotics | Other: Intervention Group 2: Infant Formula with prebiotics<br>* Infants will receive infant formula during the first 6 months of life<br>|
| Active Comparator: Control Group 1: Standard Infant Formula (CS-born)<br>CS born infants, randomized to receive standard infant formula without synbiotics | Other: Control Group 1 and 2: Infant Formula without synbiotics<br>* Infants will receive infant formula during the first 6 months of life<br>|
| Active Comparator: Control Group 2 : Standard Infant Formula (VD-born)<br>VD born infants, receiving standard infant formula without synbiotics (self-selected for formula-feeding = non-randomized) | Other: Control Group 1 and 2: Infant Formula without synbiotics<br>* Infants will receive infant formula during the first 6 months of life<br>|
| No Intervention: Reference Group 1: Breastfed (CS-born)<br>CS-born infants, receiving exclusive breast-feeding with mother's own breast milk (non-randomized) | |
| No Intervention: Reference Group 2: Breastfed (VD-born)<br>VD-born infants, receiving exclusive breast-feeding with mother's own breast milk (non-randomized) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment whether an infant formula containing synbiotics positively affects the composition of the gut microbiota in CS-born infants compared to a standard formula (without synbiotics) or breast-feeding within the first 6 months of life |  | 6 months duration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Caesarean Section; Microbiota; Infant Formula; Infants