Cesarean Section, Fecal Microbiota Transplantation, Overweight and Obesity
Conditions
Keywords
Fecal Microbiota Transplantation, Cesarean Section, Overweight and Obesity
Brief summary
This single-center randomized controlled trial evaluates whether donor-derived fecal microbiota transplantation (FMT) administered within 6 hours after birth can improve gut microbiota development and reduce the risk of immune-mediated and metabolic diseases in infants born by elective cesarean delivery. Newborns are randomized 1:1 to receive either donor-derived FMT or standard postnatal care. Participants are followed through 36 months of age with stool samples, questionnaires, growth assessments, and health data collection, with registry-based follow-up continuing until 10 years of age.
Detailed description
This is a single-center, randomized, controlled trial conducted at Oulu University Hospital, Finland. The study aims to investigate whether administration of donor-derived microbiota transplantation shortly after birth can modify gut microbiota development and reduce the risk of immune-mediated and metabolic diseases among children born by elective cesarean delivery. Pregnant women aged 18 to 49 years scheduled for elective cesarean delivery at term are contacted by a study nurse approximately one week before the planned delivery. Interested families receive detailed information about the study, and written informed consent is obtained before delivery. Eligible newborns are randomized in a 1:1 ratio using block randomization to either the intervention group or the control group. Infants in the intervention group receive microbiota transplantation from a healthy female donor selected from the study microbiota bank within 6 hours after birth. Infants in the control group receive standard postnatal care without microbiota transplantation. Maternal exclusion criteria include age below 18 or above 49 years, multiple pregnancy, regular use of immunosuppressive biological medication, diagnosed immunodeficiency in the mother or a first-degree relative of the unborn child, and known or suspected major congenital structural anomalies or immunodeficiency in the fetus. Infant exclusion criteria include preterm birth (\<37 completed weeks of gestation), birth weight \<2500 g, admission to a neonatal intensive care unit, requirement for respiratory support, or need for systemic antibiotic treatment before administration of the intervention. Participants are followed longitudinally from birth through early childhood. Follow-up assessments include stool sample collection, questionnaires, growth measurements, and health data obtained from medical records and national health registries. Study visits and data collection are performed at predefined time points from birth to 36 months of age. Long-term follow-up using registry-based data will continue until 10 years of age, subject to parental consent. The primary outcome is a composite endpoint comprising any autoimmune disease, allergic disease, obstructive respiratory disease requiring specialized healthcare, and overweight or obesity. Secondary outcomes include gut microbiota composition and development, growth trajectories, immunological outcomes, and individual disease endpoints. The original protocol included an additional study arm in which infants could receive a maternal fecal microbiota transplantation from their own mother. This study arm was subsequently removed from the protocol. The protocol amendment was reviewed and approved by the Wellbeing Services County of North Ostrobothnia (Pohde) Research Ethics Committee prior to implementation. The planned sample size is approximately 460 participants. The sample size calculation was based on an assumed prevalence of 20% for the composite primary outcome and was powered to detect a reduction to 10% in the intervention group, with a two-sided significance level of 0.05 and 80% statistical power.
Interventions
DIETARY_SUPPLEMENTDonor-derived fecal microbiota transplantation
A fecal microbiota transplantation prepared from stool donated by a healthy female donor from the study microbiota bank is administered orally to the newborn within 6 hours after birth following elective cesarean delivery.
Sponsors
Oulu University Hospital
University of Oulu
University of Turku
Turku University Hospital
University of Helsinki
Academy of Finland
Biocenter Oulu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Masking description
The research statistician performs the computer-generated randomization. The study nurse prepares the fecal transplant according to the randomization. Study participants or investigators are not aware of study group.
Intervention model description
Eligible newborns are randomized 1:1 using block randomization to receive either donor-derived fecal microbiota transplantation or standard postnatal care. The two groups are followed in parallel and compared with respect to microbiota development, growth, and health outcomes during childhood.
Eligibility
Sex/Gender
ALL
Age
0 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
Pregnant women aged 18 to 49 years Scheduled for elective cesarean delivery at term (≥37 completed weeks of gestation) Willing and able to provide written informed consent Infant eligible for study participation following birth
Exclusion criteria
(Mother): Age \<18 years or \>49 years Multiple pregnancy Regular use of immunosuppressive biological medication Diagnosed immunodeficiency in the mother Diagnosed immunodeficiency in a first-degree relative of the unborn child Known or suspected major congenital structural anomaly in the fetus Known or suspected fetal immunodeficiency Previous participation in the SISU-FMT study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite incidence of immune-mediated and metabolic disorders | Birth to 10 years of age | Incidence of a composite outcome including any autoimmune disease, allergic disease, obstructive respiratory disease requiring specialized healthcare, and overweight or obesity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The source of colonization by exclusively shared genes (ESGs) | 3 month of age | Is the microbiota vertically transmitted from mother or does fecal transplant alter the microbiota measured by ESGs, which are defined as genes that are found in only 2 individuals of all subjects. In the study, the nucleotide sequences of ESGs are required to be 100% identical. As such, ESGs are strong indicators of the transmission of species and genes from one subject to another. If a single species is found in 2 individuals (1 mother, 1 infant) who have ≥1 ESG that belongs to this species, the species is considered a transmitted species. |
| Microbial composition profiles in fecal sample | Until 12 months of age | The difference in microbial composition profiles in fecal sample between the infants in different study groups, specifically diversity and relative abundances of different bacteria phyla and species. |
| Height in centimeters | 10 years of age | The difference in growth in height between the infants in different study groups |
| Weight-for-length (%) | 10 years of age | The difference in growth in weight in infants the infants in different study groups |
| Weight in kilograms | 10 years of age | The difference in growth in weight in infants the infants in different study groups |
| Height z-score | 10 years of age | The difference in growth in height between the infants in different study groups |
| Incidence of allergic diseases | Birth to 10 years of age | Incidence of physician-diagnosed allergic diseases identified from healthcare records and national registries. |
| Incidence of obstructive respiratory disease | Birth to 10 years of age | Incidence of obstructive respiratory diseases requiring treatment in specialized healthcare. |
| Incidence of autoimmune diseases | Birth to 10 years of age | Incidence of physician-diagnosed autoimmune diseases identified from healthcare records and national registries. |
Countries
Finland
Contacts
CONTACTMarika Paalanne, MD, PhD
CONTACTTerhi Ruuska-Loewald, Professor
PRINCIPAL_INVESTIGATORTerhi Ruuska-Loewald, Professor
Oulu Univeristy Hospital
STUDY_DIRECTORMarika Paalanne, MD, PhD
Oulu Univeristy Hospital
Outcome results
None listed