A Randomized, Blinded, Controlled Trial to Evaluate Effects of Multi-strain Bacillus Spore Probiotic Supplements (LiveSpo PREG-MOM and LiveSpo CONSY) on Growth Metrics, Prevention of Functional Gastrointestinal Disorders, and Modulation of the Gut Microbiota in Cesarean-Delivered Neonates
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Anabio R&D
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Change in stool frequency
Study Overview
Brief Summary
Infants born by cesarean section commonly show early weight loss and slower recovery of birth weight, together with characteristic patterns of gut microbiota dysbiosis marked by reduced Bifidobacterium and Bacteroides and increased Proteobacteria. This early microbial alteration has been associated with functional gastrointestinal disorders (FGIDs), including colic, regurgitation, and changes in stool frequency and consistency, which may in turn affect early growth and overall gastrointestinal functioning. Probiotic supplementation is considered a safe and feasible strategy to support microbial restoration and improve digestive function during the first months of life.
In this study, researchers propose that daily supplementation with multi-strain Bacillus spore probiotics may help support healthy early growth, reduce functional gastrointestinal symptoms, and promote a more balanced gut microbiota in cesarean-delivered infants.
The objective of this study is to evaluate the safety and efficacy of two oral probiotic formulations, LiveSpo PREG-MOM and LiveSpo CONSY, containing multi-strain B. subtilis ANA46, B. clausii ANA39, and B. coagulans ANA40 at respective 3 and 4 billion colony-forming units (CFU)/5 mL ampoule, administered 1 ampoule daily, during the first 90 days of life. The study examines effects on growth, digestive symptoms, immune markers, and microbial composition.
Study Design: This randomized, blind, controlled clinical trial will enroll 180 healthy full-term cesarean-born infants at Hanoi Obstetrics and Gynecology Hospital.
Intervention Description: Participants will be randomly assigned to three groups (n = 60 each). All groups will receive one 5-mL ampoule daily for 90 days: LiveSpo PREG-MOM, LiveSpo CONSY, or placebo. Stool samples will be collected at several follow-up time points to assess digestive health and microbial development. All products will be provided in blinded and coded packaging to maintain objectivity.
Study Duration: 12 months
Detailed Description
Infants delivered by cesarean section commonly experience early differences in feeding and distinct patterns of gut microbial development compared with infants born vaginally. Because cesarean delivery limits contact with maternal vaginal microbiota, which is an important source of early microbial transfer, these infants often show delayed establishment of key early colonizers. Multiple cohort studies have documented lower abundances of beneficial genera such as Bifidobacterium and Bacteroides, along with relatively higher proportions of Proteobacteria during the first months of life. This shift in microbial composition has been associated with functional gastrointestinal symptoms in early infancy, including regurgitation, colic, abdominal discomfort, and changes in stool frequency and consistency. Such symptoms can affect feeding patterns, contribute to variations in weight gain, and influence overall gastrointestinal functioning during the neonatal period. As cesarean delivery rates continue to rise in Vietnam, there is increasing interest in supportive approaches that may help promote gastrointestinal functioning and healthier gut microbial development in this group.
Probiotic supplementation during early infancy has been explored as a potential strategy to support gut microbial maturation. Spore-forming Bacillus strains, belonging to safe B. subtilis, B. clausii, and B. coagulans species, are notable for their stability and ability to survive passage through the digestive tract. These characteristics allow them to reach the intestine in viable form, where they may interact with the developing gut ecosystem. Prior pediatric studies of Bacillus preparations have reported favorable safety profiles and signals of benefit for digestive conditions, although findings vary depending on strain and study design. Multi-strain products may offer complementary biological functions, providing broader support for the developing gut environment.
Based on this scientific background, the present study has been designed to evaluate two oral Bacillus spore probiotic formulations of B. subtilis ANA46, B. clausii ANA39, and B. coagulans ANA40, LiveSpo PREG-MOM (3 billion spores per 5 mL) and LiveSpo CONSY (4 billion spores per 5 mL), in cesarean-delivered infants. The study aims to evaluate whether daily supplementation during the first 90 days of life influences early growth trajectories, the occurrence of functional gastrointestinal disturbances, immune indicators in stool, and the development of gut microbial communities. The study will also assess the presence of probiotic spores in stool as an indicator of product use compliance.
This investigation is a randomized, blind, controlled clinical trial conducted at Hanoi Obstetrics and Gynecology Hospital. A total of 180 healthy full-term infants (38-40 weeks' gestation) delivered by cesarean section will be enrolled after parental consent. Eligible infants will be randomly assigned in equal numbers to one of three groups: Placebo (RO water), Pregmom (LiveSpo PREG-MOM), or Consy (LiveSpo CONSY). Randomization will use permuted blocks to help maintain balanced allocation across groups, and all products will be provided in identical coded ampoules to ensure blinding of families, clinical staff, and laboratory personnel.
Participants will receive one 5-mL ampoule of the assigned product once daily for 90 days. Clinical assessments will be performed at baseline and on days 2, 9, 30, 60, and 90. These assessments include measurements of weight, length, and head circumference, along with documentation of digestive patterns such as stool frequency, stool characteristics, regurgitation…, using structured observation tools suitable for young infants.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 0 Days to 1 Day (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy term neonates delivered by cesarean section.
- •Infants were born at term, ranging from 38 to 40 weeks' gestation.
- •Birth weight appropriate for gestational age (AGA), defined as between the 10th and 90th percentiles for gestational age (≥P10 and ≤P90).
- •The infant's parent(s) or legal guardian(s) provide written informed consent and agree to comply with study procedures.
Exclusion Criteria
- •For the neonate:
- •Multiple births (twins, triplets, etc.)
- •Birth weight outside the appropriate-for-gestational-age range: small for gestational age (SGA, < P10) or large for gestational age (LGA, > P90).
- •Major congenital abnormalities affecting the hematologic, hepatobiliary, cardiovascular, renal/urinary, or gastrointestinal systems; severe inborn errors of metabolism; or suspected primary immunodeficiency.
- •Prior exposure to systemic or enteral antibiotics (oral, IV, or IM) before the baseline assessment.
- •Known allergy or intolerance to any component of the investigational product.
- •Concurrent participation in another interventional clinical trial.
- •The investigators judge the neonate to be unsuitable for participation.
- •Parent(s) or legal guardian(s) who do not comply with study requirements or refuse to sign the informed consent.
- •For the mother:
- •Mother diagnosed with a serious or unstable medical condition involving the hepatobiliary, renal/urinary, cardiovascular, respiratory, endocrine/metabolic, or psychiatric systems.
- •Mother who intends to use, or is prescribed, any other probiotic/prebiotic product for herself or the infant during the study period.
Arms & Interventions
Placebo group
The Placebo group receives reverse osmosis (RO) water with a dosage of 1 ampoule per day for 90 days.
Intervention: RO water (Other)
Pregmom group
The Pregmom group receives RO water plus B. subtilis, B. clausii, and B. coagulans at 3 billion CFU/5 mL (LiveSpo PREG-MOM) with a dosage of 1 ampoule per day for 90 days.
Intervention: LiveSpo PREG-MOM (Combination Product)
Consy group
The Consy group receives RO water plus B. subtilis, B. clausii, and B. coagulans at 4 billion CFU/5 mL (LiveSpo CONSY) with a dosage of 1 ampoule per day for 90 days.
Intervention: LiveSpo CONSY (Combination Product)
Outcomes
Primary Outcomes
Change in stool frequency
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in daily stool frequency compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in stool consistency (Diapered Infant Stool Scale score)
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in stool consistency using the Diapered Infant Stool Scale (type 1-type 5) compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in regurgitation
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in regurgitation assessed by both frequency (number of regurgitation episodes per day) and severity (caregiver-reported severity), compared with baseline (day 0). Measurements will be obtained at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in crying episodes
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in the number of crying episodes per day compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in stool frequency
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in daily stool frequency compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in stool consistency (Diapered Infant Stool Scale score)
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in stool consistency using the Diapered Infant Stool Scale (type 1-type 5) compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in regurgitation
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in regurgitation assessed by both frequency (number of regurgitation episodes per day) and severity (caregiver-reported severity), compared with baseline (day 0). Measurements will be obtained at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Change in crying episodes
Time Frame: Days 0, 2, 9, 30, 60, and 90
Change in the number of crying episodes per day compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.
Secondary Outcomes
- Immune indicators in stool (cytokines and IgA)(Days 0, 9, and 30)
- Gut microbiota composition(Days 0 and 30)
- Change in infant body weight(Days 0, 2, 9, 30, 60, and 90)
- Change in infant body length(Days 0, 30, 60, and 90)
- Change in infant head circumference(Days 0, 30, 60, and 90)
- Immune indicators in stool (cytokines and IgA)(Days 0, 9, and 30)
- Gut microbiota composition(Days 0 and 30)