Health Outcomes in C-Section Infants With Fecal Microbiota Transplantation

Официальное название

Section-Born Infants and SUccessful Health Outcomes After Fecal Microbiota Transplantation (SISU-FMT)

Обзор

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.

Подробное описание

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.

Вмешательства

• Пищевая добавка Donor-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.

Первичные конечные точки

• Composite incidence of immune-mediated and metabolic disorders [Срок оценки: Birth to 10 years of age]

Вторичные конечные точки (9)

• The source of colonization by exclusively shared genes (ESGs) [Срок оценки: 3 month of age]
• Microbial composition profiles in fecal sample [Срок оценки: Until 12 months of age]
• Height in centimeters [Срок оценки: 10 years of age]
• Weight-for-length (%) [Срок оценки: 10 years of age]
• Weight in kilograms [Срок оценки: 10 years of age]
• Height z-score [Срок оценки: 10 years of age]
• Incidence of allergic diseases [Срок оценки: Birth to 10 years of age]
• Incidence of obstructive respiratory disease [Срок оценки: Birth to 10 years of age]
• Incidence of autoimmune diseases [Срок оценки: Birth to 10 years of age]

Критерии участия

Критерии включения

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

Exclusion Criteria (Infant):

Preterm birth (<37 completed weeks of gestation) Birth weight <2500 g Admission to a neonatal intensive care unit prior to the intervention Requirement for respiratory support prior to the intervention Requirement for systemic antibiotic treatment prior to the intervention

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Финляндия · 1 центр

• Oulu University Hospital — Oulu

Публикации

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• Korpela K, Renko M, Vanni P, Paalanne N, Salo J, Tejesvi MV, Koivusaari P, Ojaniemi M, Pokka T, Kaukola T, Pirttila AM, Tapiainen T. Microbiome of the first stool and overweight at age 3 years: A prospective cohort study. Pediatr Obes. 2020 Nov;15(11):e12680. doi: 10.1111/ijpo.12680. Epub 2020 Jul 7. PMID 32638554
• Cho NA, Sales KM, Sampsell K, Wang W, Noye Tuplin EW, Lowry DE, Reimer RA. C-section birth increases offspring obesity risk dependent on maternal diet and obesity status in rats. Obesity (Silver Spring). 2021 Oct;29(10):1664-1675. doi: 10.1002/oby.23258. Epub 2021 Aug 31. PMID 34464518
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• Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr. 2008 Oct;88(4):894-9. doi: 10.1093/ajcn/88.4.894. PMID 18842773
• Ainonen S, Tejesvi MV, Mahmud MR, Paalanne N, Pokka T, Li W, Nelson KE, Salo J, Renko M, Vanni P, Pirttila AM, Tapiainen T. Antibiotics at birth and later antibiotic courses: effects on gut microbiota. Pediatr Res. 2022 Jan;91(1):154-162. doi: 10.1038/s41390-021-01494-7. Epub 2021 Apr 6. PMID 33824448
• Betran AP, Ye J, Moller AB, Souza JP, Zhang J. Trends and projections of caesarean section rates: global and regional estimates. BMJ Glob Health. 2021 Jun;6(6):e005671. doi: 10.1136/bmjgh-2021-005671. PMID 34130991
• Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A, Simpson N, Kumar N, Stares MD, Rodger A, Brocklehurst P, Field N, Lawley TD. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019 Oct;574(7776):117-121. doi: 10.1038/s41586-019-1560-1. Epub 2019 Sep 18. PMID 31534227

Идентификаторы

NCT: NCT06282952 · 183/2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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